bluuebunny/crossref_metadata_2025_split huggingface dataset:
Defining the AHR-regulated transcriptome in NK cells reveals gene expression programs relevant to development and function
Authors: Trikha Prashant , Moseman Jena E. , Thakkar Aarohi , Campbell Amanda R. , Elmas Ezgi , Foltz Jennifer A. , Chakravarti Nitin , Fitch James R. , Mardis Elaine R. , Lee Dean A. 
Published: September 2021

AbstractThe aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that regulates cellular processes in cancer and immunity, including innate immune cell development and effector function. However, the transcriptional repertoire through which AHR mediates these effects remains largely unexplored. To elucidate the transcriptional elements directly regulated by AHR in natural killer (NK) cells, we performed RNA and chromatin immunoprecipitation sequencing on NK cells exposed to AHR agonist or antagonist. We show that mature peripheral blood NK cells lack AHR, but its expression is induced by Stat3 during interleukin-21–driven activation and proliferation, coincident with increased NCAM1 (CD56) expression resulting in a CD56bright phenotype. Compared with control conditions, NK cells expanded in the presence of the AHR antagonist, StemRegenin-1, were unaffected in proliferation or cytotoxicity, had no increase in NCAM1 transcription, and maintained the CD56dim phenotype. However, it showed altered expression of 1004 genes including those strongly associated with signaling pathways. In contrast, NK cells expanded in the presence of the AHR agonist, kynurenine, showed decreased cytotoxicity and altered expression of 97 genes including those strongly associated with oxidative stress and cellular metabolism. By overlaying these differentially expressed genes with AHR chromatin binding, we identified 160 genes directly regulated by AHR, including hallmark AHR targets AHRR and CYP1B1 and known regulators of phenotype, development, metabolism, and function such as NCAM1, KIT, NQO1, and TXN. In summary, we define the AHR transcriptome in NK cells, propose a model of AHR and Stat3 coregulation, and identify potential pathways that may be targeted to overcome AHR-mediated immune suppression.
The binding of autotaxin to integrins mediates hyperhomocysteinemia-potentiated platelet activation and thrombosis in mice and humans
Authors: Han Lulu , Miao Yutong , Zhao Yang , Zhang Xingzhong , Ma Xiaolong , Du Xing , Kong Wei , Xu Qingbo , Liu Junling , Dai Kesheng , Feng Juan , Wang Xian 
Published: September 2021

Abstract
Hyperhomocysteinemia (HHcy) is associated with an exaggerated platelet thrombotic response at sites of vascular injury. In this study, human medical examination showed that elevated human plasma Hcy levels correlated positively with enhanced blood coagulation and platelet activity, suggesting that humans with HHcy are more prone to thrombus formation at the sites of vascular injury. Accordingly, we observed accelerated platelet activation, primary hemostasis, and thrombus formation in apolipoprotein E-deficient (ApoE−/−) mice with acute or chronic HHcy. Upon homocysteine (Hcy) administration in C57BL/6J mice, platelet aggregation, spreading and clot retraction were markedly induced. More important, Hcy increased the affinity of platelet integrin αIIbβ3 with ligands and enhanced integrin outside-in signaling by promoting membrane phosphatidylserine exposure in vitro. Mechanistically, lipidomics analysis showed that lysophosphatidylcholines were the primary metabolites leading to clustering of HHcy-stimulated platelets. Cytosolic phospholipase A2 (cPLA2) activity and autotaxin (ATX, a secreted lysophospholipase D) secretion were upregulated by Hcy, leading to membrane phospholipid hydrolysis and PS exposure. Moreover, secreted ATX directly interacted with integrin β3. Inhibitors of cPLA2 and ATX activity blocked integrin αIIbβ3 outside-in signaling and thrombosis in HHcy ApoE−/− mice. In this study, we identified a novel mechanism by which HHcy promotes platelet membrane phospholipid catabolism and extracellular ATX secretion to activate integrin outside-in signaling, consequently exacerbating thrombosis and the results revealed an innovative approach to treating HHcy-related thrombotic diseases.
Calcitonin receptor-like (CALCRL) is a marker of stemness and an independent predictor of outcome in pediatric AML
Authors: Angenendt Linus , Wöste Marius , Mikesch Jan-Henrik , Arteaga Maria Francisca , Angenendt Adrian , Sandmann Sarah , Berdel Wolfgang E. , Lenz Georg , Dugas Martin , Meshinchi Soheil , Schliemann Christoph , Rössig Claudia 
Published: September 2021

Abstract
We have recently identified the G protein-coupled neuropeptide receptor calcitonin receptor-like (CALCRL) as an independent prognostic biomarker and a therapeutic target in more than 1500 adult patients with acute myeloid leukemia (AML). Here, we confirmed CALCRL expression as a prognostic factor in a cohort of 284 pediatric patients with AML. High CALCRL expression was independently associated with event-free survival (hazard ratio [HR], 1.87; 95% confidence interval [CI], 1.36-2.57; P = .0001), overall survival (HR, 1.55; 95% CI, 1.06-2.27; P = .025), and cumulative incidence of relapse (HR, 2.10; 95% CI, 1.49-1.96; P &lt; .0001) when adjusting for age, white blood cell count, and genetic risk. Despite its association with leukemia stem cell signatures, CALCRL expression remained associated with all end points when compared with the 17-gene leukemic stem cell score. The strong association of CALCRL expression with the risk of relapse also in the pediatric population supports its role as novel age-independent master regulator of relapse-initiating, drug-tolerant AML cells in humans.
Clinical impact of NPM1-mutant molecular persistence after chemotherapy for acute myeloid leukemia
Authors: Tiong Ing S. , Dillon Richard , Ivey Adam , Kuzich James A. , Thiagarajah Nisha , Sharplin Kirsty M. , Kok Chung Hoow , Tedjaseputra Aditya , Rowland James P. , Grove Carolyn S. , Abro Emad , Shortt Jake , Hiwase Devendra K. , Bajel Ashish , Potter Nicola E. , Smith Matthew L. , Hemmaway Claire J. , Thomas Abin , Gilkes Amanda F. , Russell Nigel H. , Wei Andrew H. 
Published: September 2021

Abstract
Monitoring of NPM1 mutant (NPM1mut) measurable residual disease (MRD) in acute myeloid leukemia (AML) has an established role in patients who are treated with intensive chemotherapy. The European LeukemiaNet has defined molecular persistence at low copy number (MP-LCN) as an MRD transcript level &lt;1% to 2% with a &lt;1-log change between any 2 positive samples collected after the end of treatment (EOT). Because the clinical impact of MP-LCN is unknown, we sought to characterize outcomes in patients with persistent NPM1mut MRD after EOT and identify factors associated with disease progression. Consecutive patients with newly diagnosed NPM1mut AML who received ≥2 cycles of intensive chemotherapy were included if bone marrow was NPM1mut MRD positive at the EOT, and they were not transplanted in first complete remission. One hundred patients were followed for a median of 23.5 months; 42% remained free of progression at 1 year, either spontaneously achieving complete molecular remission (CRMRD−; 30%) or retaining a low-level NPM1mut transcript (12% for ≥12 months and 9% at last follow-up). Forty percent met the criteria for MP-LCN. Preemptive salvage therapy significantly prolonged relapse-free survival. Risk factors associated with disease progression were concurrent FLT3-internal tandem duplication at diagnosis and suboptimal MRD response (NPM1mut reduction &lt;4.4-log) at EOT.
The antimicrobial peptide S100A8/A9 produced by airway epithelium functions as a potent and direct regulator of macrophage phenotype and function
Authors: Skronska-Wasek Wioletta , Durlanik Sibel , Le Huy Quang , Schroeder Victoria , Kitt Kerstin , Garnett James Peter , Pflanz Stefan 
Published: September 2021

BackgroundElevated counts of alveolar macrophages and attenuated phagocytic capacity are associated with chronic obstructive pulmonary disease (COPD). Factors governing macrophage phagocytosis are poorly understood. In this study we aimed to compare the influence of airway epithelial cell secretions from individuals with COPD and without COPD (non-COPD) on macrophage phagocytic activity, and the role of antimicrobial peptides (AMPs).MethodsSupernatants from non-COPD and COPD small airway epithelial cell (SAEC) cultures exposed to non-typeableHaemophilus influenzae(NTHi) were applied to human monocyte-derived macrophages (MDMs) to assess their influence on phagocytosis. SAECs were analysed for changes in AMP expression by quantitative reverse transcription PCR, and the influence of select AMPs on macrophage phenotype and function was assessed by flow cytometry and metabolic activity assay.ResultsSecretions from the apical and basolateral surface of NTHi-exposed SAECs from non-COPD donors elicited superior phagocytic capacity in MDMs. Moreover, NTHi exposure led to a rapid increase in the expression of a range of AMPs by non-COPD SAECs, but this response was delayed in COPD SAECs. We demonstrate that treatment with AMPs β-defensin 2 and S100 calcium binding protein A8/S100 calcium binding protein A9 (S100A8/A9) improved the phagocytic capacity of MDMs. In-depth analysis of the influence of S100A8/A9 on MDMs revealed a role for this AMP in macrophage phenotype and function. Furthermore, we show that the expression of S100A8 and S100A9 is directly regulated by WNT/β-catenin signalling, a known deregulated pathway in COPD.ConclusionIn conclusion, for the first time, we demonstrate that airway epithelium from patients with COPD has a reduced capacity to support the phagocytic function of macrophages in response to acute NTHi exposure, and we identify the WNT/β-catenin signalling-modulated and epithelium-derived S100A8/A9 as a potent regulator of macrophage phenotype and function.
Quantification of aerosol dispersal from suspected aerosol-generating procedures
Authors: Strand-Amundsen Runar , Tronstad Christian , Elvebakk Ole , Martinsen Tormod , Dybwad Marius , Lingaas Egil , Tønnessen Tor Inge 
Published: September 2021

BackgroundOxygen-delivering modalities like humidified high-flow nasal cannula (HFNC) and noninvasive positive-pressure ventilation (NIV) are suspected of generating aerosols that may contribute to transmission of disease such as coronavirus disease 2019. We sought to assess if these modalities lead to increased aerosol dispersal compared to the use of non-humidified low-flow nasal cannula oxygen treatment (LFNC).MethodsAerosol dispersal from 20 healthy volunteers using HFNC, LFNC and NIV oxygen treatment was measured in a controlled chamber. We investigated effects related to coughing and using a surgical face mask in combination with the oxygen delivering modalities. An aerodynamic particle sizer measured aerosol particles (APS3321, 0.3–20 µm) directly in front of the subjects, while a mesh of smaller particle sensors (SPS30, 0.3–10 µm) was distributed in the test chamber.ResultsNon-productive coughing led to significant increases in particle dispersal close to the face when using LFNC and HFNC but not when using NIV. HFNC or NIV did not lead to a statistically significant increase in aerosol dispersal compared to LFNC. With non-productive cough in a room without air changes, there was a significant drop in particle levels between 100 cm and 180 cm from the subjects.ConclusionsOur results indicate that using HFNC and NIV does not lead to increased aerosol dispersal compared to low-flow oxygen treatment, except in rare cases. For a subject with non-productive cough, NIV with double-limb circuit and non-vented mask may be a favourable choice to reduce the risk for aerosol spread.
Associations of childhood unintentional injuries with maternal emotional status during COVID-19
Authors: Guo Xiangrong , Hua Hui , Xu Jian , Liu Zhiwei 
Published: September 2021

Abstract
Background
To explore the characteristics of unintentional childhood-injury during the COVID-19 pandemic and assess the association of unintentional-injury with maternal emotional status.

Methods
A cross-sectional survey was conducted with a convenience sample of 1300 children under 12-years-old from 21 schools (including nurseries/ kindergartens/ primary schools) in Wuhan and Shanghai during March to April 2020, and the mothers completed questionnaires online. Self-rating Depression/Anxiety Scales were used to evaluate maternal emotional status, questions on child unintentional-injury were based on the International-Statistical-Classification-of-Diseases-and-Related-Health-Problems-version-10 (ICD-10), and a total of 11 kinds of unintentional injuries were inquired. Information on socio-demographic and family-background factors was also collected.

Results
The children of 0–4, 5–9, and 10–12 years accounted for 29.2, 55.2 and 15.6%, respectively, the unintentional-injury rates were 10.29, 4.18 and 3.45%, respectively (P < 0.001), and boys had higher rates than girls. The three leading causes included “being struck by/against”, falls and animal bites (traffic-injury accounted for a small proportion). Lower maternal educational, living in suburban/rural (vs. urban) areas, grandparents (vs. mothers) being main caregivers, more child exposure to secondhand smoke, close relatives being suspected/ confirmed COVID-19 cases were associated with a higher risk of child unintentional-injury. After adjusting for related confounders, higher maternal depression levels were associated with a higher risk of unintentional injury.

Conclusions
The characteristics of unintentional childhood injury were different from those in non-pandemic periods. The main causes, risk factors and the association of unintentional injury with maternal depression deserve attention for development of effective measures for preventing children from unintentional injury during COVID-19 pandemic.

Graphical abstract
Test@work: evaluation of workplace HIV testing for construction workers using the RE-AIM framework
Authors: Jones Wendy , Somerset Sarah , Evans Catrin , Whittingham Katharine , Middleton Matthew , Blake Holly 
Published: September 2021

Abstract
Background
Community testing for HIV can reach previously untested populations but is rarely offered in workplaces. Targeting the construction sector could reach workers from high risk populations.

Methods
The RE-AIM framework was used to evaluate Test@Work, a workplace HIV testing intervention for construction workers implemented at 21 events (10 companies) in the UK.
Test@Work had three components: 1) an online health toolkit to inform managers about health screening and HIV testing; 2) general health checks; and 3) opt-in HIV consultation and testing. Quantitative data were collected using registration and exit questionnaires with workers (n = 426) and pre/post-event questionnaires with managers (n = 15), with qualitative analysis of free text responses.

Results
Reach 426 individuals had health checks. Participants were broadly representative of the UK construction workforce, but with a higher proportion of permanent workers. Most workers reported being in good health but also believed their work had an adverse impact on their health. Effectiveness: 97% of health check participants opted to have a consultation about sexual health (n = 413) and 82% had an HIV test (n = 348), of whom 78% had not previously been tested. All HIV tests were non-reactive. HIV testing at work was considered acceptable by most participants. Participants reported learning new things about their health (74%), said they would make changes as a result (70%) and felt confident of success (median score 8/10). Adoption: Recruitment of companies was challenging and time consuming. Seven of the participating companies were very large, employing over 1000 workers, which is atypical of construction generally. Implementation: All events were completed as planned and were considered successful by all parties. Maintenance: All managers would arrange further events if they were offered them. Six managers incorporated sexual health awareness into their health programmes, but this was not possible for many as health agendas were set centrally by their organisations.

Conclusions
Opt-in HIV testing, when embedded within a general health check, has high uptake and acceptability in the UK construction sector, and reaches individuals at risk for HIV who may not otherwise attend for testing. Cost-effectiveness of this approach is yet to be determined.

Trial registration
ClinicalTrials.gov Identifier: NCT04292002.
A community-engaged approach to understanding environmental health concerns and solutions in urban and rural communities
Authors: Wang Suwei , Richardson Molly B. , Evans Mary B. , Johnson Ethel , Threadgill-Matthews Sheryl , Tyson Sheila , White Katherine L. , Gohlke Julia M. 
Published: September 2021

Abstract
Background
Focus groups and workshops can be used to gain insights into the persistence of and potential solutions for environmental health priorities in underserved areas. The objective of this study was to characterize focus group and workshop outcomes of a community-academic partnership focused on addressing environmental health priorities in an urban and a rural location in Alabama between 2012 and 2019.

Methods
Six focus groups were conducted in 2016 with 60 participants from the City of Birmingham (urban) and 51 participants from Wilcox County (rural), Alabama to discuss solutions for identified environmental health priorities based on previous focus group results in 2012. Recorded focus groups were transcribed and analyzed using the grounded theory approach. Four follow-up workshops that included written survey instruments were conducted to further explore identified priorities and determine whether the priorities change over time in the same urban (68 participants) and rural (72 participants) locations in 2018 and 2019.

Results
Consistent with focus groups in 2012, all six focus groups in 2016 in Birmingham identified abandoned houses as the primary environmental priority. Four groups listed attending city council meetings, contacting government agencies and reporting issues as individual-level solutions. Identified city-level solutions included city-led confiscation, tearing down and transferring of abandoned property ownership. In Wilcox County, all six groups agreed the top priority was drinking water quality, consistent with results in 2012. While the priority was different in Birmingham versus Wilcox County, the top identified reason for problem persistence was similar, namely unresponsive authorities. Additionally, individual-level solutions identified by Wilcox County focus groups were similar to Birmingham, including contacting and pressuring agencies and developing petitions and protesting to raise awareness, while local policy-level solutions identified in Wilcox County included government-led provision of grants to improve septic systems, and transparency in allocation of funds. Workshops in 2018 and 2019 further emphasized water quality as the top priority in Wilcox County, while participants in Birmingham transitioned from abandoned houses as a top priority in 2018 to drinking water quality as a new priority in 2019.

Conclusions
Applying a community-engaged approach in both urban and rural locations provided better understanding of the unique opportunities and challenges for identifying potential interventions for environmental health priorities in both locations. Results can help inform future efforts to address locally defined environmental health issues and solutions.
Anomalous insertion of anterior and posterior horns of medial meniscus. Case report
Authors: Mariani Pier Paolo , Battaglia Michael J , Torre Guglielmo 
Published: September 2021

Abstract
Background
Anatomical variations of the attachment of medial meniscus are a common finding. However, anomalies of the posterior horn are extremely rare. Only two cases of posterior root anomaly have been described prior to the routine use of arthroscopy for evaluation and treatment of meniscal pathology. In this report, we present an anomaly of both the anterior and posterior roots of the medial meniscus that posed both a diagnostic and therapeutic dilemma.

Case presentation
The patient is young male soccer player who is currently 16 years of age and began having the atraumatic onset of pain and symptoms that limited performance starting at age 14 and was referred for failure of response to nonoperative treatment. Diagnostic arthroscopy revealed the presence of an anteromedial meniscofemoral ligament whereas the posterior root showed no bony attachment. The radiographic and arthroscopic findings are described. The clinical decision was made after to proceed with observation, reassurance, and gradual return to full activity with physiotherapy guidance.

Discussion and conclusion
The absence of injury, the mild complaints reported by the patient, his age, skeletal immaturity, and remaining growth led us to adopt a conservative approach to treating this anatomic variant and currently the patient is able to participate fully in sports without symptoms or restrictions.
Society, family, and individual characteristics as double-edged swords in the social reintegration of Iranian female survivors from unintentional severe burns: a qualitative study of enablers and barriers
Authors: Hemmati Maslakpak Masumeh , Ajoudani Fardin , Lotfi Mojgan , Alinejad Vahid 
Published: September 2021

AbstractBackgroundReintegrating to society is a significant challenge during burn survivors’ rehabilitation.AimThis study aims to describe what Iranian female survivors from unintentional severe burns experience as enablers and barriers of social reintegration (SR).MethodsFourteen adult female burn survivors whose burns were unintentional participated in this qualitative study. Data were gathered through semi-structured face-to-face or telephone interviews and analyzed using inductive content analysis.ResultsThirteen subcategories and six categories were emerged. Categories and subcategories of enablers content area were as follows: positive impact of society on SR (normal treatment of society, instrumental support), positive impact of family on SR (magnifying personal abilities assets, empathy and emotional support), and positive impact of personal characteristics on SR (coping with others stares, right to have a normal social life). Categories and subcategories of Barriers content area were as follows: negative impact of society on SR (being questioned in public, incorrect judgment about intent of burns, burns as a contagious disease), negative impact of family on SR (embarrassment of appearing in public with the survivor, family mistrust), and negative impact of intra-personal factors on SR (exaggeration of the post-burn changes, being over-sensitive to the others looks). From the deep interpretation of the data two overarching themes were emerged: “acceptance of the new normal by the society and the individual” and “being encompassed by misconceptions and mistreatments”.ConclusionsSociety, family and the individual characteristics have a dual role to play in the success of social reintegration in Iranian female unintentional burn survivors.