bluuebunny/crossref_metadata_2025_split huggingface dataset:
Platelet-derived extracellular vesicles infiltrate and modify the bone marrow during inflammation
Authors: French Shauna L. , Butov Kirill R. , Allaeys Isabelle , Canas Jorge , Morad Golnaz , Davenport Patricia , Laroche Audrée , Trubina Natalia M. , Italiano Joseph E. , Moses Marsha A. , Sola-Visner Martha , Boilard Eric , Panteleev Mikhail A. , Machlus Kellie R. 
Published: July 2020

AbstractDuring inflammation, steady-state hematopoiesis switches to emergency hematopoiesis to repopulate myeloid cells, with a bias toward the megakaryocytic lineage. Soluble inflammatory cues are thought to be largely responsible for these alterations. However, how these plasma factors rapidly alter the bone marrow (BM) is not understood. Inflammation also drives platelet activation, causing the release of platelet-derived extracellular vesicles (PEVs), which package diverse cargo and reprogram target cells. We hypothesized that PEVs infiltrate the BM, providing a direct mode of communication between the plasma and BM environments. We transfused fluorescent, wild-type (MPL+) platelets into recipient cMpl−/−mice before triggering systemic inflammation. Twenty hours postinfusion, we observed significant infiltration of donor platelet-derived particles in the BM, which we tracked immunophenotypically (MPL+ immunohistochemistry staining) and quantified by flow cytometry. To determine if this phenomenon relates to humans, we extensively characterized both megakaryocyte-derived and PEVs generated in vitro and in vivo, and found enrichment of extracellular vesicles in bone marrow compared with autologous peripheral blood. Last, BM from cMpl−/− mice was cultured in the presence or absence of wild-type (MPL+) PEVs. After 72 hours, flow cytometry revealed increased megakaryocytes only in cultures with added PEVs. The majority of CD41+ cells were bound to PEVs, suggesting a PEV-mediated rescue of megakaryopoiesis. In conclusion, we report for the first time that plasma-residing PEVs infiltrate the BM. Further, PEVs interact with BM cells in vivo and in vitro, causing functional reprogramming that may represent a novel model of inflammation-induced hematopoiesis.
Late molecular recurrences in patients with chronic myeloid leukemia experiencing treatment-free remission
Authors: Rousselot Philippe , Loiseau Clémence , Delord Marc , Cayuela Jean Michel , Spentchian Marc 
Published: July 2020

Abstract
Treatment-free remission (TFR) is an opportunity for patients with chronic myeloid leukemia (CML). Reported cumulative incidence curves of molecular recurrence (MRec) arbor a 2-phase shape with mainly early events, but also some late events (late MRec [LMRec]). Having discontinued our first patient in 2004, we have access to a prolonged follow-up, enabling us to characterize these late events. Over 15 years, 128 patients from our institution were registered in the Stop Imatinib (STIM; A Study for Tyrosine Kinase Inhibitors Discontinuation [A-STIM]) trial. MRec was defined by the loss of major molecular response (BCR-ABL1IS &gt;0.1%). At the first TFR attempt, patients had been taking a tyrosine kinase inhibitor for a median of 7.1 years and in BCR-ABL1IS ≤0.01% (MR4) for a median of 4 years. The median follow-up of patients in TFR was 6.5 years. The TFR rate was estimated to be 45.6% after 7 years. For 9/65 (14%) patients experiencing MRec, recurrence occurred after 2 years in TFR (median, 3.6 years). The residual rate of MRec after 2 years was estimated to be 18%. The probability of remaining in TFR was 65.4% for patients having experienced fluctuations of their minimal residual disease (MRD) (at least 2 consecutive measurements BCR-ABL1IS &gt;0.0032% or loss of MR4), whereas it was 100% for those with stable MRD (P = .003). After 2 years in TFR, we observed an 18% residual rate of LMRec. These late events represent 14% of all MRec and occur in patients with fluctuating MRD measurements. A long-term molecular follow-up therefore remains mandatory for CML patients in TFR. The A-STIM study was registered at www.clinicaltrials.gov as #NCT02897245.
SABRTooth: a randomised controlled feasibility study of stereotactic ablative radiotherapy (SABR) with surgery in patients with peripheral stage I nonsmall cell lung cancer considered to be at higher risk of complications from surgical resection
Authors: Franks Kevin N. , McParland Lucy , Webster Joanne , Baldwin David R. , Sebag-Montefiore David , Evison Matthew , Booton Richard , Faivre-Finn Corinne , Naidu Babu , Ferguson Jonathan , Peedell Clive , Callister Matthew E.J. , Kennedy Martyn , Hewison Jenny , Bestall Janine , Gregory Walter M. , Hall Peter , Collinson Fiona , Olivier Catherine , Naylor Rachel , Bell Sue , Allen Peter , Sloss Andrew , Snee Michael 
Published: July 2020

ObjectivesStereotactic ablative radiotherapy (SABR) is a well-established treatment for medically inoperable peripheral stage I nonsmall cell lung cancer (NSCLC). Previous nonrandomised evidence supports SABR as an alternative to surgery, but high-quality randomised controlled trial (RCT) evidence is lacking. The SABRTooth study aimed to establish whether a UK phase III RCT was feasible.Design and methodsSABRTooth was a UK multicentre randomised controlled feasibility study targeting patients with peripheral stage I NSCLC considered to be at higher risk of surgical complications. 54 patients were planned to be randomised 1:1 to SABR or surgery. The primary outcome was monthly average recruitment rates.ResultsBetween July 2015 and January 2017, 318 patients were considered for the study and 205 (64.5%) were deemed ineligible. Out of 106 (33.3%) assessed as eligible, 24 (22.6%) patients were randomised to SABR (n=14) or surgery (n=10). A key theme for nonparticipation was treatment preference, with 43 (41%) preferring nonsurgical treatment and 19 (18%) preferring surgery. The average monthly recruitment rate was 1.7 patients against a target of three. 15 patients underwent their allocated treatment: SABR n=12, surgery n=3.ConclusionsWe conclude that a phase III RCT randomising higher risk patients between SABR and surgery is not feasible in the National Health Service. Patients have pre-existing treatment preferences, which was a barrier to recruitment. A significant proportion of patients randomised to the surgical group declined and chose SABR. SABR remains an alternative to surgery and novel study approaches are needed to define which patients benefit from a nonsurgical approach.
Cyclophilin inhibitors restrict Middle East respiratory syndrome coronavirusviainterferon-λin vitroand in mice
Authors: Sauerhering Lucie , Kupke Alexandra , Meier Lars , Dietzel Erik , Hoppe Judith , Gruber Achim D. , Gattenloehner Stefan , Witte Biruta , Fink Ludger , Hofmann Nina , Zimmermann Tobias , Goesmann Alexander , Nist Andrea , Stiewe Thorsten , Becker Stephan , Herold Susanne , Peteranderl Christin 
Published: July 2020

While severe coronavirus infections, including Middle East respiratory syndrome coronavirus (MERS-CoV), cause lung injury with high mortality rates, protective treatment strategies are not approved for clinical use.We elucidated the molecular mechanisms by which the cyclophilin inhibitors cyclosporin A (CsA) and alisporivir (ALV) restrict MERS-CoV to validate their suitability as readily available therapy in MERS-CoV infection.Calu-3 cells and primary human alveolar epithelial cells (hAECs) were infected with MERS-CoV and treated with CsA or ALV or inhibitors targeting cyclophilin inhibitor-regulated molecules including calcineurin, nuclear factor of activated T-cells (NFATs) or mitogen-activated protein kinases. Novel CsA-induced pathways were identified by RNA sequencing and manipulated by gene knockdown or neutralising antibodies. Viral replication was quantified by quantitative real-time PCR and 50% tissue culture infective dose. Data were validated in a murine MERS-CoV infection model.Both CsA and ALV reduced MERS-CoV titres and viral RNA replication in Calu-3 cells and hAECs, improving epithelial integrity. While neither calcineurin nor NFAT inhibition reduced MERS-CoV propagation, blockade of c-Jun N-terminal kinase diminished infectious viral particle release but not RNA accumulation. Importantly, CsA induced interferon regulatory factor 1 (IRF1), a pronounced type III interferon (IFNλ) response and expression of antiviral genes. Downregulation of IRF1 or IFNλ increased MERS-CoV propagation in the presence of CsA. Importantly, oral application of CsA reduced MERS-CoV replicationin vivo, correlating with elevated lung IFNλ levels and improved outcome.We provide evidence that cyclophilin inhibitors efficiently decrease MERS-CoV replicationin vitroandin vivo viaupregulation of inflammatory antiviral cell responses, in particular IFNλ. CsA might therefore represent a promising candidate for treating MERS-CoV infection.
Vitamin C to pregnant smokers persistently improves infant airway function to 12 months of age: a randomised trial
Authors: McEvoy Cindy T. , Shorey-Kendrick Lyndsey E. , Milner Kristin , Schilling Diane , Tiller Christina , Vuylsteke Brittany , Scherman Ashley , Jackson Keith , Haas David M. , Harris Julia , Park Byung S. , Vu Annette , Kraemer Dale F. , Gonzales David , Bunten Carol , Spindel Eliot R. , Morris Cynthia D. , Tepper Robert S. 
Published: July 2020

BackgroundVitamin C (500 mg·day−1) supplementation for pregnant smokers has been reported to increase newborn pulmonary function and infant forced expiratory flows (FEFs) at 3 months of age. Its effect on airway function through 12 months of age has not been reported.ObjectiveTo assess whether vitamin C supplementation to pregnant smokers is associated with a sustained increased airway function in their infants through 12 months of age.MethodsThis is a pre-specified secondary outcome of a randomised, double-blind, placebo-controlled trial that randomised 251 pregnant smokers between 13 and 23 weeks of gestation: 125 to 500 mg·day−1vitamin C and 126 to placebo. Smoking cessation counselling was provided. FEFs performed at 3 and 12 months of age were analysed by repeated-measures analysis of covariance.ResultsFEFs were performed in 222 infants at 3 months and 202 infants at 12 months of age. The infants allocated to vitamin C had significantly increased FEFs over the first year of life compared to those allocated to placebo. The overall increased flows were 40.2 mL·s−1for at FEF75(75% of forced vital capacity (FVC)) (adjusted 95% CI for difference 6.6–73.8; p=0.025); 58.3 mL·s−1for FEF50(10.9–105.8; p=0.0081); and 55.1 mL·s−1for FEF25–75(9.7–100.5; p=0.013).ConclusionsIn offspring of pregnant smokers randomised to vitamin Cversusplacebo, vitamin C during pregnancy was associated with a small but significantly increased airway function at 3 and 12 months of age, suggesting a potential shift to a higher airway function trajectory curve. Continued follow-up is underway.
P2X7 receptors exert a permissive effect on the activation of presynaptic AMPA receptors in rat trigeminal caudal nucleus glutamatergic nerve terminals
Authors: Currò Diego , Navarra Pierluigi , Samengo Irene , Martire Maria 
Published: July 2020

Abstract
Background
Purine receptors play roles in peripheral and central sensitization and are associated with migraine headache. We investigated the possibility that ATP plays a permissive role in the activation of AMPA receptors thus inducing Glu release from nerve terminals isolated from the rat trigeminal caudal nucleus (TCN).

Methods
Nerve endings isolated from the rat TCN were loaded with [3H]D-aspartic acid ([3H]D-ASP), layered into thermostated superfusion chambers, and perfused continuously with physiological medium, alone or with various test drugs. Radioactivity was measured to assess [3H]D-ASP release under different experimental conditions.

Results
Synaptosomal [3H]D-ASP spontaneous release was stimulated by ATP and to an even greater extent by the ATP analogue benzoylbenzoylATP (BzATP). The stimulation of [3H]D-ASP basal release by the purinergic agonists was prevented by the selective P2X7 receptor antagonist A438079. AMPA had no effect on basal [3H]D-ASP release, but the release observed when synaptosomes were exposed to AMPA plus a purinoceptor agonist exceeded that observed with ATP or BzATP alone. The selective AMPA receptor antagonist NBQX blocked this “excess” release. Co-exposure to AMPA and BzATP, each at a concentration with no release-stimulating effects, evoked a significant increase in [3H]D-ASP basal release, which was prevented by exposure to a selective AMPA antagonist.

Conclusions
P2X7 receptors expressed on glutamatergic nerve terminals in the rat TCN can mediate Glu release directly and indirectly by facilitating the activation of presynaptic AMPA receptors. The high level of glial ATP that occurs during chronic pain states can promote widespread release of Glu as well as can increase the function of AMPA receptors. In this manner, ATP contributes to the AMPA receptor activation involved in the onset and maintenance of the central sensitization associated with chronic pain.
A Chronicle on Genetics and the March of Darwinian and Mendelian Medicine
Authors: Govindaraju Diddahally R. 
Published: July 2020

AbstractKen Burns, a well-known documentarian has produced a film titled, “The Gene: An Intimate History” based on Siddhartha Mukherjee’s book by the same name. The film focuses sharply on the history of genetics, the science of inheritance and variation, in particular, the gene, the central player in genetics, its discovery, structure and function as well as its myriad influence on development, growth, health, disease and evolution of all organisms. Importantly, he has shown how geneticists, physicians, patients and their families as well as society at large must cooperate, develop mutual trust and share ethical responsibilities in order to predict, prevent, manage and cure many inherited disorders. Mr. Burns has reinforced these ideas beautifully with illustrations, archived film footage, location filming and commentaries. The film also hints at the need for taking a unified Darwinian-Mendelian and Hippocratic approach toward building a healthier human society. In short, this is a beautiful and engrossing documentary on the future of Genetic Medicine.
Tuberculin skin test conversion in patients under treatment with anti-tumor necrotizing factor alpha agents
Authors: Hejazi Mohammad-Esmaeil , Ahmadzadeh Atefeh , Khabbazi Alireza , Ebrahimi Aliasghar , Farmani Maryam , Hejazi Yasin 
Published: July 2020

Abstract
Background
Despite successful clinical outcomes of biologic medications in patients with chronic rheumatic diseases, some considerable adverse effects such as infections remain a major concern. Possibility of tuberculosis (TB) reactivation over treatment with anti-tumor necrotizing factor (TNF) alpha agents has necessitated a screening test before initiation of treatment. However, screening over the course of treatment is not recommended in those patients with negative baseline screening tests. This study aimed to evaluate the efficacy of tuberculin skin test (TST) before treatment in patients with chronic rheumatologic diseases who were indicated to receive anti-TNF-alpha therapy and the necessity of repeating this test over the course of treatment.

Methods
In this prospective study, patients with chronic rheumatologic diseases receiving anti-TNF-alpha agents were studied in a two-year period. TST was performed before treatment and those with positive results were excluded from the study. Thereafter, treatment with anti-TNF-alpha agents was initiated with the indicated dose. TST was repeated before administration of biologic treatment until TST became positive or 16 weeks after the initiation of treatment with anti-TNF-alpha.

Results
A total of 51 cases were studied, of whom one patient (1.9%) was excluded due to positive TST before treatment. All participants received infliximab and the TST test became positive in one patient (2%) 2 weeks after receiving the first dose. Also, the results of further tests at weeks 6, 10, and 14 were all negative for the remaining patients.

Conclusion
Due to the possibility of TST conversion after administration of anti-TNF-alpha therapy, it is important to consider TB monitoring in patients under treatment with these agents using available methods such as TST.
The impact on quality of life from informing diagnosis in patients with cancer: a systematic review and meta-analysis
Authors: Wan Miao , Luo Xianggui , Wang Juan , Mvogo Ndzana Louis. B , Chang Chen , Li Zhenfen , Zhang Jianglin 
Published: July 2020

Abstract
Background
The aim of this study was to assess the impact on quality of life from informing patients with cancer of their diagnosis and disease status.

Method
We searched the follow databases, PubMed, CENTRAL (Cochrane Central Register of Controlled Trials), PsycINFO, WEB OF SCIENCE, Embase, CBM (Chinese Biomedical Literature database), WANFANG database (Chinese Medicine Premier), and CNKI (China National Knowledge Infrastructure), using the following terms: neoplasm, cancer, tumor, tumor, carcinoma, disclosure, truth telling, breaking bad news, knowledge, knowing, awareness, quality of life, QOL. Pairs of reviewers independently screened documents and extracted the data, and the meta-analysis was performed using Revman 5.0 software.

Results
Eleven thousand seven hundred forty records retrieved from the databases and 23 studies were included in the final analysis. A meta-analysis revealed that there were no differences in either the general quality of life and symptoms of fatigue, pain, dyspnea, insomnia, appetite loss, and diarrhea, between informed and uniformed cancer patients (P > 0.05). There were also no differences found between the patient groups in physical function, role function, cognitive activity, and emotional function (P > 0.05). In terms of vitality, patients who were completely informed about their diagnosis showed higher vitality than uniformed patients. Uninformed patients seemed to have lower social function scores. Between partly informed and uninformed cancer patients, no differences were found in their general quality of life, function domains, and disease-related symptoms (P > 0.05).

Conclusion
Informing cancer patients of their diagnosis may not have a detrimental effect on their quality of life.

Trial registration
CRD42017060073.
“Bariatric families”- a new phenomenon with unique characteristics
Authors: Weiss Netta , Kalamitzky Nataly , Interator Hagar , Lubetzky Ronit , Moran-Lev Hadar 
Published: July 2020

Abstract
Background
Many obese children have at least one obese parent, and some of them have one parent who had undergone bariatric surgery (“bariatric families”). The perceptions and attitudes towards child obesity of parents in bariatric families vs. non-bariatric families have not been explored. We assessed how parents who underwent bariatric surgery for obesity perceived their child’s obesity compared to those perceptions of obese parents who did not undergo bariatric surgery.

Methods
We conducted a cross-sectional survey by interviewing families in which one or both parents underwent bariatric surgery (bariatric group) and comparing their responses to those of families in which one or both parents had been treated conservatively for obesity (control group). The children of both groups were attending the Obesity Clinic of our children’s hospital.

Results
Thirty-six children (median age 10.6 years, 18 in each group, matched for age and sex) were recruited. More parents in the bariatric group replied that weight plays an important role in determining self-image (p < 0.03), and more replied that their child’s obesity is a current and future health problem (p < 0.03 and p < 0.007, respectively, Table 1). Five children (28%) in the bariatric group had expectations of undergoing bariatric surgery compared to none in the control group (p < 0.02), with a similar trend among their parents (44% vs. 11%, respectively, p < 0.07).

Conclusion
Families in which one or both parents underwent bariatric surgery for obesity revealed different perceptions of their child’s obesity and different opinions about interventions for treating it compared to families with no bariatric surgery.
“Knock Knock”: a qualitative study exploring the experience of household contacts on home visits and their attitude towards people living with TB in South Africa
Authors: Sathar Farzana , Velen Kavindhran , Peterson Meaghan , Charalambous Salome , Chetty-Makkan Candice M. 
Published: July 2020

Abstract
Background
Household contract tracing (HHCT) is an important strategy for active tuberculosis case finding and offers an opportunity for testing of other diseases such as HIV. However, there is limited data on the patient-centered approach to HHCT. Our study aimed to describe experiences and preferences of household contacts (HHCs) for HHCT.

Methods
We conducted a qualitative study in Rustenburg, South Africa from September 2013 to March 2015. Twenty-four HHCs (≥18 years) had audio-recorded in-depth interviews. We used an inductive thematic analysis approach to develop themes. We made an a priori assumption that we would reach saturation with at least 20 interviews.

Results
There were 16 (66.7%) females (median age = 36 years) and eight (33.3%) males (median age = 34 years). Two themes developed: (i) Positive attitude of HHCs towards TB services provided at home and (ii) HHCs relationship to and acceptance of people living with TB (PLTB). The first main theme emphasized that HHCs appreciated the home visits. Participants preferred home visits because they had negative experiences at the clinic such as delayed waiting times and long queues. HHCs supported the screening of children for TB at home. Participants suggested that the research staff could expand their services by screening for diabetes and hypertension alongside TB screening. In the second main theme, there was a sense of responsibility from the HHCs towards accepting the diagnosis of PLTB and caring for them. A sub-theme that emerged was that as their knowledge on TB disease improved, they accepted the TB status of the PLTB empowering them to take care of the PLTB.

Conclusions
HHCs are supportive of HHCT and felt empowered by receiving TB education that ultimately allowed them to better understand and care for PLTB. HHCs were supportive of screening children for TB at home. Future HHCT activities should consider raising community awareness on the benefits of TB contact tracing at households.