bluuebunny/crossref_metadata_2025_split huggingface dataset:
The RNA m6A Reader YTHDF1 Is Required for Acute Myeloid Leukemia Progression
Authors: Hong Yun-Guang , Yang Zhigang , Chen Yan , Liu Tian , Zheng Yuyuan , Zhou Chun , Wu Guo-Cai , Chen Yinhui , Xia Juan , Wen Ruiting , Liu Wenxin , Zhao Yi , Chen Jin , Gao Xiangwei , Chen Zhanghui 
Published: January 2023

AbstractN6-methyladenosine (m6A), the most abundant modification in mRNAs, has been defined as a crucial modulator in the progression of acute myelogenous leukemia (AML). Identification of the key regulators of m6A modifications in AML could provide further insights into AML biology and uncover more effective therapeutic strategies for patients with AML. Here, we report overexpression of YTHDF1, an m6A reader protein, in human AML samples at the protein level with enrichment in leukemia stem cells (LSC). Whereas YTHDF1 was dispensable for normal hematopoiesis in mice, depletion of YTHDF1 attenuated self-renewal, proliferation, and leukemic capacity of primary human and mouse AML cells in vitro and in vivo. Mechanistically, YTHDF1 promoted the translation of cyclin E2 in an m6A-dependent manner. Structure-based virtual screening of FDA-approved drugs identified tegaserod as a potential YTHDF1 inhibitor. Tegaserod blocked the direct binding of YTHDF1 with m6A-modified mRNAs and inhibited YTHDF1-regulated cyclin E2 translation. Moreover, tegaserod reduced the viability of patient-derived AML cells in vitro and prolonged survival in patient-derived xenograft models. Together, our study defines YTHDF1 as an integral regulator of AML progression by regulating the expression of m6A-modified mRNAs, which might serve as a potential therapeutic target for AML.Significance:The m6A reader YTHDF1 is required for progression of acute myelogenous leukemia and can be targeted with the FDA-approved drug tegaserod to suppress leukemia growth.
Olig1/2-Expressing Intermediate Lineage Progenitors Are Predisposed to PTEN/p53-Loss–Induced Gliomagenesis and Harbor Specific Therapeutic Vulnerabilities
Authors: Verma Ravinder , Chen Xiameng , Xin Dazhuan , Luo Zaili , Ogurek Sean , Xin Mei , Rao Rohit , Berry Kalen , Lu Q. Richard 
Published: January 2023

AbstractMalignant gliomas such as glioblastoma are highly heterogeneous with distinct cells of origin and varied genetic alterations. It remains elusive whether the specific states of neural cell lineages are differentially susceptible to distinct genetic alterations during malignant transformation. Here, an analysis of The Cancer Genome Atlas databases revealed that comutations of PTEN and TP53 are most significantly enriched in human high-grade gliomas. Therefore, we selectively ablated Pten and Trp53 in different progenitors to determine which cell lineage states are susceptible to malignant transformation. Mice with PTEN/p53 ablation mediated by multilineage-expressing human GFAP (hGFAP) promoter–driven Cre developed glioma but with incomplete penetrance and long latency. Unexpectedly, ablation of Pten and Trp53 in Nestin+ neural stem cells (NSC) or Pdgfra+/NG2+ committed oligodendrocyte precursor cells (OPC), two major cells of origin in glioma, did not induce glioma formation in mice. Strikingly, mice lacking Pten and Trp53 in Olig1+/Olig2+ intermediate precursors (pri-OPC) prior to the committed OPCs developed high-grade gliomas with 100% penetrance and short latency. The resulting tumors exhibited distinct tumor phenotypes and drug sensitivities from NSC- or OPC-derived glioma subtypes. Integrated transcriptomic and epigenomic analyses revealed that PTEN/p53-loss induced activation of oncogenic pathways, including HIPPO-YAP and PI3K signaling, to promote malignant transformation. Targeting the core regulatory circuitries YAP and PI3K signaling effectively inhibited tumor cell growth. Thus, our multicell state in vivo mutagenesis analyses suggests that transit-amplifying states of Olig1/2 intermediate lineage precursors are predisposed to PTEN/p53-loss–induced transformation and gliomagenesis, pointing to subtype-specific treatment strategies for gliomas with distinct genetic alterations.Significance:Multiple progenitor-state mutagenesis reveal that Olig1/2-expressing intermediate precursors are highly susceptible to PTEN/p53-loss–mediated transformation and impart differential drug sensitivity, indicating tumor-initiating cell states and genetic drivers dictate glioma phenotypes and drug responses.See related commentary by Zamler and Hu, p. 807
Experimental Validation of Float Array Tidal Current Measurements in Agate Pass, Washington
Authors: Harrison Trevor W. , Clemett Nate , Polagye Brian , Thomson Jim 
Published: January 2023

Abstract
Tidal currents, particularly in narrow channels, can be challenging to characterize due to high current speeds (>1 m s−1), strong spatial gradients, and relatively short synoptic windows. To assess tidal currents in Agate Pass, Washington, we cross evaluated data products from an array of acoustically tracked underwater floats and from acoustic Doppler current profilers (ADCPs) in both station-keeping and drifting modes. While increasingly used in basin-scale science, underwater floats have seen limited use in coastal environments. This study presents the first application of a float array toward small-scale (<1 km), high-resolution (<5 m) measurements of mean currents in energetic tidal channel and utilizes a new prototype float, the μFloat, designed specifically for sampling in dynamic coastal waters. We show that a float array (20 floats) can provide data with similar quality to ADCPs, with measurements of horizontal velocity differing by less than 10% of nominal velocity, except during periods of low flow (0.1 m s−1). Additionally, floats provided measurements of the three-dimensional temperature field, demonstrating their unique ability to simultaneously resolve in situ properties that cannot be remotely observed.

Significance Statement
The purpose of this research was to validate measurements of tidal currents in a fast-flowing tidal channel using a prototype technology composed of 20 drifting underwater sensors called μFloats (“microFloats”) and five surface buoys against standard devices (acoustic Doppler current profilers). Float measurements matched those from the standard devices within 10% of the mean water speed and simultaneously provided three-dimensional mapping of temperature in the test region. Results demonstrate how moderate numbers of simultaneously deployed μFloats can provide high-resolution sensing capacity that will improve our understanding of physical, chemical, and biological processes in coastal waters.
Using the Grooved Pegboard Test as an Embedded Validity Indicator in a Mixed Neuropsychiatric Sample with Varying Cognitive Impairment: Cross-Validation Problems
Authors: Chang Fini , Cerny Brian M. , Tse Phoebe Ka Yin , Rauch Andrew A. , Khan Humza , Phillips Matthew S. , Fletcher Noah B. , Resch Zachary J. , Ovsiew Gabriel P. , Jennette Kyle J. , Soble Jason R. 
Published: January 2023

Embedded validity indicators (EVIs) derived from motor tests have received less empirical attention than those derived from tests of other neuropsychological abilities, particularly memory. Preliminary evidence suggests that the Grooved Pegboard Test (GPB) may function as an EVI, but existing studies were largely conducted using simulators and population samples without cognitive impairment. In this study we aimed to evaluate the GPB’s classification accuracy as an EVI among a mixed clinical neuropsychiatric sample with and without cognitive impairment. This cross-sectional study comprised 223 patients clinically referred for neuropsychological testing. GPB raw and T-scores for both dominant and nondominant hands were examined as EVIs. A known-groups design, based on ≤1 failure on a battery of validated, independent criterion PVTs, showed that GPB performance differed significantly by validity group. Within the valid group, receiver operating characteristic curve analyses revealed that only the dominant hand raw score displayed acceptable classification accuracy for detecting invalid performance (area under curve [AUC] = .72), with an optimal cut-score of ≥106 seconds (33% sensitivity/88% specificity). All other scores had marginally lower classification accuracy (AUCs = .65–.68) for differentiating valid from invalid performers. Therefore, the GPB demonstrated limited utility as an EVI in a clinical sample containing patients with bona fide cognitive impairment.
Cascade of Care for Hepatitis C Virus Infection Among Young Adults Who Inject Drugs in a Rural County in New Mexico
Authors: Carmody Mary D. , Wagner Katherine , Bizstray Birgitta , Thornton Karla , Fiuty Phillip , Rosario Aubrey Del , Teshale Eyasu , Page Kimberly 
Published: January 2023

Objective: Treatment for hepatitis C virus (HCV) infection is highly effective; however, people who inject drugs (PWID), the population most affected by HCV, may encounter barriers to treatment. We examined the cascade of care for HCV infection among young adult PWID in northern New Mexico, to help identify gaps and opportunities for HCV treatment intervention. Methods: Young adults (aged 18-29 y) who self-reported injection drug use in the past 90 days were tested for HCV antibodies (anti-HCV) and HCV RNA. We asked participants with detectable RNA to participate in an HCV education session, prior to a referral to a local health care provider for treatment follow-up, and to return for follow-up HCV testing quarterly for 1 year. We measured the cascade of care milestones ranging from the start of screening to achievement of sustained virologic response (SVR). Results: Among 238 participants, the median age was 26 years and 133 (55.9%) were men. Most (90.3%) identified as Hispanic. Of 109 RNA-positive participants included in the cascade of care assessment, 84 (77.1%) received their results, 82 (75.2%) participated in the HCV education session, 61 (56.0%) were linked to care through a medical appointment, 27 (24.8%) attended the HCV treatment appointment, 13 (11.9%) attended their follow-up appointment, 6 (5.5%) initiated treatment, 3 (2.8%) completed treatment, and 1 (0.9%) achieved SVR. Conclusions: We observed a steeply declining level of engagement at each milestone step of the cascade of care after detection of HCV infection, resulting in a suboptimal level of HCV treatment and cure. Programs that can streamline testing and expand access to treatment from trusted health care providers are needed to improve the engagement of PWID in HCV treatment.
The Association Between Frailty and a Nurse-Identified Need for Comprehensive Geriatric Assessment Referral from the Emergency Department
Authors: Mowbray Fabrice I. , Ellis Brittany , Schumacher Connie , Heckman George , de Wit Kerstin , Strum Ryan P. , Jones Aaron , Correia Rebecca H. , Mercier Eric , Costa Andrew P. 
Published: January 2023

Background Emergency nurses commonly conduct geriatric assessments in the emergency department (ED). However, little is known about what geriatric syndromes or clinical presentations prompt a nurse to document an identified need for comprehensive geriatric assessment (CGA). Objectives To examine the association between geriatric syndromes, like frailty, and a nurse-identified need for a CGA following emergency care. Methods We conducted a secondary analysis of a multi-province Canadian cohort from the InterRAI Multinational Cohort Study. We collected data at ED registration from patients 75 years of age and older (n = 2,274) from eight ED sites across Canada between November 2009 and April 2012. Geriatric syndromes were assessed by trained emergency nurses using the interRAI ED Contact Assessment; and we retrospectively calculated the ED frailty index. We employed binary logistic regression to determine the adjusted associations between geriatric syndromes and a nurse-identified need for a CGA. Results Approximately one-quarter (28%) of older adults were identified to need a CGA following emergency care. A 0.1 unit increase in the ED frailty index increased the likelihood of a nurse identify a need for CGA (RD: 6.6; 95% CI = 5.5–7.9). Most geriatric syndromes increased the probability of a nurse documenting the need for a CGA. Conclusion When assessed by emergency nurses, the identified need for CGA is strongly linked to the presence of geriatric syndromes, including frailty. We provide face validity for the continued use of emergency nurses for screening and assessing older ED patients.
Anti-SARS-CoV-2 antibodies following vaccination are associated with lymphocyte count and serum immunoglobulins in SLE
Authors: Reynolds John A , Faustini Sian E , Tosounidou Sofia , Plant Tim , Ubhi Mandeep , Gilman Rebecca , Richter Alex G , Gordon Caroline 
Published: January 2023

Objectives Patients with Systemic Lupus Erythematosus are known to have dysregulated immune responses and may have reduced response to vaccination against COVID-19 while being at risk of severe COVID-19 disease. The aim of this study was to identify whether vaccine responses were attenuated in SLE and to assess disease- and treatment-specific associations. Methods Patients with SLE were matched by age, sex and ethnic background to healthcare worker healthy controls (HC). Anti-SARS-CoV-2 spike glycoprotein antibodies were measured at 4–8 weeks following the second COVID-19 vaccine dose (either BNT162b2 or ChAdOx1 nCoV-19) using a CE-marked combined ELISA detecting IgG, IgA and IgM (IgGAM). Antibody levels were considered as a continuous variable and in tertiles and compared between SLE patients and HC and associations with medication, disease activity and serological parameters were determined. Results Antibody levels were lower in 43 SLE patients compared to 40 HC ( p < 0.001). There was no association between antibody levels and medication, lupus disease activity, vaccine type or prior COVID infection. Higher serum IgA, but not IgG or IgM, was associated with being in a higher anti-SARS-CoV-2 antibody level tertile (OR [95% CI] 1.820 [1.050, 3.156] p = 0.033). Similarly, higher lymphocyte count was also associated with being in a higher tertile of anti-SARS-CoV-2 (OR 3.330 [1.505, 7.366] p = 0.003) Conclusion Patients with SLE have lower antibody levels following 2 doses of COVID-19 vaccines compared to HC. In SLE lower lymphocyte counts and serum IgA levels are associated with lower antibody levels post vaccination, potentially identifying a subgroup of patients who may therefore be at increased risk of infection.
Role of short-dwell daily ethanol-lock therapy in the management of hemodialysis tunneled cuffed catheter-related bloodstream infection
Authors: Gang Sishir , Konnur Abhijit , Rajapurkar Mohan , Hegde Umapati , Patel Hardik , Patel Jigar , Shete Nitiraj 
Published: January 2023

Background: Catheter-Related Blood Stream Infection (CRBSI) is the major limitation of using Tunneled cuffed catheter (TCC) for long-term Hemodialysis. The standard therapy of CRBSI involves systemic antibiotics with catheter replacement/removal. As antibiotic alone is rarely effective therapy for CRBSI, biofilm eradication using antimicrobial locking solutions is a promising modality for CRBSI treatment, hence catheter salvage. The present study evaluated the efficacy and safety of Ethanol-lock therapy (ELT) in combination with systemic antibiotics for the management of CRBSI associated with hemodialysis TCC. Method: 56 patients with CRBSI were treated with 70% ELT (1 h daily for 5 days) along with systemic antibiotics. Seventeen patients with CRBSI who didn’t consent to ELT were treated with antibiotics alone. The effect of ELT was evaluated as clinical cure (fever resolution and negative surveillance cultures), infection-free TCC survival duration and adverse events of ELT among patients with CRBSI. The parameters were compared with 17 patients treated with antibiotics alone. Results: ELT was successful in 50 out of 56 patients (89.28%); compared to 41.17% (seven out of 17) with antibiotics alone ( p < 0.001). Mean TCC survival was also significantly higher with ELT combined with systemic antibiotics (126.23 ± 18.67 days) compared to antibiotics alone (38.76 ± 9.91) ( p = 0.006). No systemic adverse effects were noted with ELT; two patients receiving ELT had catheter breakage during the study period. Conclusion: We conclude that short-dwell daily ELT with systemic antibiotics is an effective therapy for CRBSI in hemodialysis patients with TCC.
Plasma neurofilament light chain in children with relapsing MS receiving teriflunomide or placebo: A post hoc analysis of the randomized TERIKIDS trial
Authors: Kuhle Jens , Chitnis Tanuja , Banwell Brenda , Tardieu Marc , Arnold Douglas L , Rawlings Andreea M , Geertsen Svend S , Lublin Alex L , Saubadu Stephane , Truffinet Philippe , Kappos Ludwig 
Published: January 2023

Background: The phase 3 TERIKIDS study demonstrated efficacy and manageable safety for teriflunomide versus placebo in children with relapsing multiple sclerosis (RMS). Objective: Evaluate plasma neurofilament light chain (pNfL) concentrations in TERIKIDS. Methods: Patients received placebo or teriflunomide (14 mg adult equivalent) for up to 96 weeks in the double-blind (DB) period. In the open-label extension (OLE), all patients received teriflunomide until up to 192 weeks after randomization. pNfL was measured using single-molecule array assay (Simoa® NF-light™). Results: Baseline mean age was 14.5 years; 69.4% were female. Baseline geometric least square mean pNfL levels were similar for teriflunomide ( n = 78) and placebo ( n = 33) patients (19.83 vs 18.30 pg/mL). Over the combined DB and OLE periods, pNfL values were lower for teriflunomide versus placebo (analysis of variance p < 0.01; Week 192: 10.61 vs 17.32 pg/mL). Observed between-group pNfL differences were attenuated upon adjustment for gadolinium (Gd)-enhancing or new/enlarged T2 lesion counts at DB Week 24. Higher baseline pNfL levels were associated with shorter time since first MS symptom onset, higher baseline Gd-enhancing lesion counts and T2 lesion volume, and increased hazard of high magnetic resonance imaging activity or clinical relapse during the DB period. Conclusion: Teriflunomide treatment was associated with significantly reduced pNfL levels in children with RMS. ClinicalTrials.gov identifier: NCT02201108.
Current concepts in the treatment of first-time patella dislocation in children and adolescents
Authors: Sinikumpu Jaakko , Nicolaou Nicolas 
Published: January 2023

Background: Lateral dislocation of the patella is a common injury in children. It can occur in previously healthy and anatomically normal knees, but there are several abnormalities that predispose to patellar instability. Magnetic resonance imaging is an essential part of assessing for associated injuries and risk of further instability. Treatment aims to prevent redislocation, residual instability, osteoarthritis, and allow return to previous activities. The purpose of this review was to assess evidence for management of first-time patella dislocation in children and adolescents. Methods: Literature review was performed, accompanied by the current best practice by the authors. Results: Non-operative treatment is preferred, except where there are associated injuries such as osteochondral fractures that would benefit from surgery. The exact method of ideal non-operative management is not clearly defined but should focus on restoration of range of movement and strength with bracing as indicated. There seems to be a trend toward operative intervention that may well be inappropriate. Conclusion: Further prospective studies are required with focus on the younger patient to fully understand if there is an at-risk group that would benefit from early surgery. Level of evidence: level III.
Designing a mobile health smokeless tobacco cessation intervention in Odisha, India: User and provider perspectives
Authors: Panda Rajmohan , Lahoti Supriya , Mishra Arti , Prabhu Rajath R , Das Sangeeta , Satapathy Durga Madhab , Nazareth Irwin 
Published: January 2023

Objective There is limited evidence on the development of mobile health (mHealth) interventions for smokeless tobacco (SLT) cessation, despite its widespread use in South Asia. This formative qualitative study explored the perceptions of tobacco users and healthcare providers (HCPs) regarding developing a mHealth intervention for SLT cessation. Methods This was a qualitative study using in-depth interviews (IDIs) with tobacco users (n = 26) and primary care physicians (PCPs) (n = 5) and focus group discussions (FGDs) with counsellors (n = 2) in four urban primary health centres (UPHCs) in Berhampur, Odisha from February to March 2020. The data were coded and analysed by two researchers using a framework analysis method. The discussion guides and initial codes were developed based on the Transtheoretical Model (TTM) of behaviour change. Results The results were elaborated under four themes: (1) Current scenario of SLT use; (2) Barriers and facilitators for quitting SLT; (3) Barriers and facilitators for mHealth counselling; and (4) Design and delivery of the proposed intervention. SLT use was prevalent in the community regardless of sociodemographic factors. Peer factors accounted for both tobacco consumption as well as considering cessation. Participants considered mobile message counselling helpful and acceptable. Not having a mobile phone and illiteracy were identified as barriers while ease of access and rising popularity of social media applications were considered facilitators to the use of mHealth for quitting tobacco. Participants preferred messages that were pictorial, short and simple, in the local language, and tailored to individual's needs. Conclusions This is the first study that provides evidence within the Indian context that the text messaging platform may be used for delivering an SLT cessation intervention. The integration of a theoretical basis and research findings from target users can guide future intervention development.
LDPE-Nanoclay films for food packaging with improved barrier properties
Authors: Barros Carolina , Miranda Sónia , Castro Olga , Carneiro OS , Machado AV 
Published: January 2023

This study focuses on the development of low-density polyethylene matrix nanocomposite films for food packaging industry and aims at improving low-density polyethylene oxygen barrier properties while maintaining other relevant characteristics, such as processability, easy post-processing, optical and mechanical properties. low-density polyethylene nanocomposites, with 1 and 2.5 wt.% nanoclay (NC) and also compatibilized with 5 wt.% polyethylene grafted with maleic anhydride (PE-g-MA), were prepared and used to produce blown films. The nanocomposites were characterized in terms of their morphology, thermal, rheological, mechanical, barrier and optical properties, through scanning electron microscopy (SEM), X-ray diffraction (XRD), differential scanning calorimetry (DSC), rheological measurements, tensile tests, water vapor transmission, oxygen permeability tests and spectrophotometry. The results demonstrated good NC dispersion in the polymer matrix and decreased oxygen permeability in the compatibilized nanocomposite films. All the other properties did not significantly change when compared to neat low-density polyethylene. Overall, the film properties were improved with the added nanoclay and PE-g-MA and, have potential for food packaging.