bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cyclophosphamide induces type I interferon and augments the number of CD44hi T lymphocytes in mice: implications for strategies of chemoimmunotherapy of cancer
Authors: Schiavoni Giovanna , Mattei Fabrizio , Di Pucchio Tiziana , Santini Stefano M. , Bracci Laura , Belardelli Filippo , Proietti Enrico 
Published: October 2019

AbstractIn a previous study, we reported that a single injection of cyclophosphamide (CTX) in tumor-bearing mice resulted in tumor eradication when the animals were subsequently injected with tumor-sensitized lymphocytes. Notably, CTX acted by inducing bystander effects on T cells, and the response to the combined CTX/adoptive immunotherapy regimen was inhibited in mice treated with antibodies to mouse interferon (IFN)–/β. In the present study, we have investigated whether CTX induced the expression of type I IFN, and we have characterized the CTX effects on the phenotype of T cells in normal mice. CTX injection resulted in an accumulation of type I IFN messenger RNA in the spleen of inoculated mice, at 24 to 48 hours, that was associated with IFN detection in the majority of the animals. CTX also enhanced the expression of the Ly-6C on spleen lymphocytes. This enhancement was inhibited in mice treated with anti–type I IFN antibodies. Moreover, CTX induced a long-lasting increase in in vivo lymphocyte proliferation and in the percentage of CD44hiCD4+ and CD44hiCD8+T lymphocytes. These results demonstrate that CTX is an inducer of type I IFN in vivo and enhances the number of T cells exhibiting the CD44hi memory phenotype. Since type I IFN has been recently recognized as the important cytokine for the in vivo expansion and long-term survival of memory T cells, we suggest that induction of this cytokine may explain at least part of the immunomodulatory effects observed after CTX treatment. Finally, these findings provide a new rationale for combined treatments with CTX and adoptive immunotherapy in cancer patients.
Growth of FasL-bearing tumor cells in syngeneic murine host induces apoptosis and toxicity in Fas+ organs
Authors: Zeytun Ahmet , Nagarkatti Mitzi , Nagarkatti Prakash S. 
Published: October 2019

AbstractIn the current study, we investigated whether the growth of FasL-bearing tumor cells would induce apoptosis and toxicity in organs that express high level of Fas. Sera from C57BL/6 +/+(wild-type) mice injected with syngeneic FasL+ tumors, LSA, or EL-4, showed significantly higher levels of soluble FasL than that from the nontumor-bearing mice. Furthermore, the soluble FasL was functional inasmuch as the sera from tumor-bearing mice were able to induce apoptosis in Fas+ but not Fas−targets. Histopathologic studies and in situ TUNEL assay to detect apoptosis were carried out in C57BL/6 +/+(Fas+) or C57BL/6 lpr/lpr (Fas−) mice injected with syngeneic LSA and EL-4 tumor cells. The morphology of the liver and thymus from tumor bearing C57BL/6 +/+ mice showed marked damage and tissue destruction. In contrast, the liver and thymus from tumor-bearing C57BL/6 lpr/lpr mice showed minimal damage. Furthermore, the tumor-bearing C57BL/6 +/+, but not the C57BL/6 lpr/lpr, mice exhibited significant apoptosis in the liver and thymus. The FasL responsible for toxicity was tumor derived rather than host derived; tumor-bearing C57BL/6 gld/gld(FasL-defective) mice also exhibited significant apoptosis in the liver and thymus. Together, these data suggested that the in vivo growth of FasL-bearing tumor cells can induce significant apoptosis and toxicity in Fas+ tissues of the host. Such toxicity may be mediated by the soluble FasL produced by tumor cells.
Dehydration of mature and immature sickle red blood cells during fast oxygenation/deoxygenation cycles: role of KCl cotransport and extracellular calcium
Authors: McGoron Anthony J. , Joiner Clinton H. , Palascak Mary B. , Claussen William J. , Franco Robert S. 
Published: October 2019

Abstract
Sickle red blood cells (RBC) become dehydrated as a consequence of potassium loss. This process depends at least partly on deoxygenation and may be influenced by the presence of oxygenation/deoxygenation cycles and the frequency of cycling. In this study, sickle RBC were subjected to approximately 180 oxygenation/deoxygenation cycles during 4 hours to evaluate RBC dehydration with cycle periods more similar to in vivo cycles than those in previous studies. A continuous-flow, steady-state apparatus circulated a dilute RBC suspension through gas-permeable silicone tubing with segments that were exposed to either nitrogen or ambient oxygen. The percentage of sickling and partial pressure of oxygen were measured by means of sampling ports in the deoxygenation and oxygenation regions. The density increase (dehydration) of young (transferrin receptor-positive) and mature (transferrin receptor-negative) RBC and the requirements for calcium and chloride were evaluated. Density increase correlated with the percentage of sickled cells at the deoxygenation sampling port and was observed only in the presence of calcium, thereby implicating the calcium-dependent potassium channel (Gardos pathway). Density increase was not dependent on the presence of chloride, making it unlikely that KCl cotransport was an important pathway under these conditions.
Continuous salt stress-induced long non-coding RNAs and DNA methylation patterns in soybean roots
Authors: Chen Rui , Li Ming , Zhang Huiyuan , Duan Lijin , Sun Xianjun , Jiang Qiyan , Zhang Hui , Hu Zheng 
Published: October 2019

Abstract

Background
Environmental stimuli can activate a series of physiological and biochemical responses in plants accompanied by extensive transcriptional reprogramming. Long non-coding RNAs (lncRNAs), as versatile regulators, control gene expression in multiple ways and participate in the adaptation to biotic and abiotic stresses.

Results
In this study, soybean seedlings were continuously cultured for 15 days with high salinity solutions started from seed germination. Strand-specific whole transcriptome sequencing and stringent bioinformatic analysis led to the identification of 3030 long intergenic non-coding RNAs (lincRNAs) and 275 natural antisense transcripts (lncNATs) in soybean roots. In contrast to mRNAs, newly identified lncRNAs exhibited less exons, similar AU content to UTRs, even distribution across the genome and low evolutionary conservation. Remarkably, more than 75% of discovered lncRNAs that were activated or up-regulated by continuous salt stress mainly targeted proteins with binding and catalytic activities. Furthermore, two DNA methylation maps with single-base resolution were generated by using reduced representation bisulfite sequencing, offering a genome-wide perspective and important clues for epigenetic regulation of stress-associated lncRNAs and protein-coding genes.

Conclusions
Taken together, our findings systematically demonstrated the characteristics of continuous salt stress-induced lncRNAs and extended the knowledge of corresponding methylation profiling, providing valuable evidence for a better understanding of how plants cope with long-term salt stress circumstances.
Intensified household contact tracing, prevention and treatment support versus enhanced standard of care for contacts of tuberculosis cases in South Africa: study protocol for a household cluster-randomised trial
Authors: MacPherson Peter , Webb Emily L. , Variava Ebrahim , Lala Sanjay G. , Milovanovic Minja , Ratsela Andrew , Lebina Limakatso , Kinghorn Anthony , Martinson Neil A. 
Published: October 2019

Abstract

Background
Household contact tracing of index TB cases has been advocated as a key part of TB control for many years, but has not been widely implemented in many low-resource setting because of the current dearth of high quality evidence for effectiveness. Innovative strategies for earlier, more effective treatment are particularly important in contexts with hyper-endemic levels of HIV, where levels of TB infection remain extremely high.

Methods
We present the design of a household cluster-randomised controlled trial of interventions aimed at improving TB-free survival and reducing childhood prevalence of Mycobacterium tuberculosis infection among household contacts of index TB cases diagnosed in two provinces of South Africa. Households of index TB cases will be randomly allocated in a 1:1 ratio to receive either an intensified home screening and linkage for TB and HIV intervention, or enhanced standard of care. The primary outcome will compare between groups the TB-free survival of household contacts over 15 months. All participants, or their next-of-kin, will provide written informed consent to participate.

Discussion
Evidence from randomised trials is required to identify cost-effective approaches to TB case-finding that can be applied at scale in sub-Saharan Africa.

Trial registration
ISRCTN16006202 (01/02/2017: retrospectively registered) and NHREC4399 (11/04/2016: prospectively registered). Protocol version: 4.0 (date: 18th January 2018).
Iranian midwives’ attitudes and beliefs toward physiological childbirth: a cross-sectional study
Authors: Sadeghzadeh Narges , Amiri-Farahani Leila , Haghani Shima , Hasanpoor-Azghady Syedeh Batool 
Published: October 2019

AbstractBackgroundThe significant role of midwives in providing labor and delivery care underscores the necessity of the identification of attitudes and beliefs of these groups of maternity care providers toward physiological childbirth. The purpose of the current study was to describe midwives’ attitudes and beliefs toward physiological childbirth and identify its related factors.MethodsThis cross-sectional study was carried out on 200 midwives working in the labor and delivery wards of selected hospitals in an urban area of Tehran, Iran, through the continuous sampling method from May to July 2018. The data were collected using a two-part demographic characteristic form and Midwives’ Attitudes and Beliefs Questionnaire-Revised toward physiological childbirth. Data analysis was performed in SPSS software (version 25). The significance level was set atP < 0.05.ResultsThe mean score of midwives’ attitudes and beliefs toward physiological childbirth were 119.90 with a standard deviation of 9.30. Moreover, of the different domains of Midwives’ Attitudes and Beliefs Questionnaire-Revised, the women’s experience of birth (78.53) and the medical model conflict (51.05) obtained the highest and lowest scores, respectively. According to the multiple linear regression model analysis, the total mean score of midwives’ attitudes and beliefs toward physiological childbirth was significantly correlated with the level of education and interest in the profession (P < 0.05). Midwives with a master degree obtained higher scores (4.32) in terms of attitudes and beliefs toward physiologic childbirth, compared to those with an associate or bachelor degree. Also, there were 0.09 increases in the attitude and belief score of midwives per one score increase in their interest in the profession. It can be concluded that these two variables explained 16% of the variation in the scores of midwives’ attitudes and beliefs to physiological childbirth.ConclusionThe results of this study showed that midwives with higher levels of education and more interest in their profession had more positive attitudes and beliefs toward physiological childbirth. Therefore, it is necessary to motivate midwives to obtain higher levels of education and increase their interest in the profession to promote physiological childbirth.
Implementing a toolkit for the prevention, management and control of carbapenemase-producing Enterobacteriaceae in English acute hospitals trusts: a qualitative evaluation
Authors: Schneider Annegret , Coope Caroline , Michie Susan , Puleston Richard , Hopkins Susan , Oliver Isabel 
Published: October 2019

Abstract

Background
Antimicrobial resistance is an increasing problem in hospitals world-wide. Following other countries, English hospitals experienced outbreaks of carbapenemase-producing Enterobacteriaceae (CPE), a bacterial infection commonly resistant to last resort antibiotics. One way to improve CPE prevention, management and control is the production of guidelines, such as the CPE toolkit published by Public Health England in December 2013. The aim of this research was to investigate the implementation of the CPE toolkit and to identify barriers and facilitators to inform future policies.

Methods
Acute hospital trusts (N = 12) were purposively sampled based on their self-assessed CPE colonisation rates and time point of introducing local CPE action plans. Following maximum variation sampling, 44 interviews with hospital staff were conducted between April and August 2017 using a semi-structured topic guide based on the Capability, Opportunity, Motivation and Behaviour Model and the Theoretical Domains Framework, covering areas of influences on behaviour. Interviews were audio-recorded, transcribed verbatim and analysed using thematic analysis.

Results
The national CPE toolkit was widely disseminated within infection prevention and control teams (IPCT), but awareness was rare among other hospital staff. Local plans, developed by IPCTs referring to the CPE toolkit while considering local circumstances, were in place in all hospitals. Implementation barriers included: shortage of isolation facilities for CPE patients, time pressures, and competing demands. Facilitators were within hospital and across-hospital collaborations and knowledge sharing, availability of dedicated IPCTs, leadership support and prioritisation of CPE as an important concern. Participants using the CPE toolkit had mixed views, appreciating its readability and clarity about patient management, but voicing concerns about the lack of transparency on the level of evidence and the practicality of implementation. They recommended regular updates, additional clarifications, tailored information and implementation guidance.

Conclusions
There were problems with the awareness and implementation of the CPE toolkit and frontline staff saw room for improvement, identifying implementation barriers and facilitators. An updated CPE toolkit version should provide comprehensive and instructive guidance on evidence-based CPE prevention, management and control procedures and their implementation in a modular format with sections tailored to hospitals’ CPE status and to different staff groups.
Semi-quantitative visual assessment of chest radiography is associated with clinical outcomes in critically ill patients
Authors: Mason Stefanie E. , Dieffenbach Paul B. , Englert Joshua A. , Rogers Angela A. , Massaro Anthony F. , Fredenburgh Laura E. , Higuera Angelica , Pinilla-Vera Mayra , Vilas Marta , San Jose Estepar Raul , Washko George R. , Baron Rebecca M. , Ash Samuel Y. 
Published: October 2019

Abstract

Background
Respiratory pathology is a major driver of mortality in the intensive care unit (ICU), even in the absence of a primary respiratory diagnosis. Prior work has demonstrated that a visual scoring system applied to chest radiographs (CXR) is associated with adverse outcomes in ICU patients with Acute Respiratory Distress Syndrome (ARDS). We hypothesized that a simple, semi-quantitative CXR score would be associated with clinical outcomes for the general ICU population, regardless of underlying diagnosis.

Methods
All individuals enrolled in the Registry of Critical Illness at Brigham and Women’s Hospital between June 2008 and August 2018 who had a CXR within 24 h of admission were included. Each patient’s CXR was assigned an opacification score of 0–4 in each of four quadrants with the total score being the sum of all four quadrants. Multivariable negative binomial, logistic, and Cox regression, adjusted for age, sex, race, immunosuppression, a history of chronic obstructive pulmonary disease, a history of congestive heart failure, and APACHE II scores, were used to assess the total score’s association with ICU length of stay (LOS), duration of mechanical ventilation, in-hospital mortality, 60-day mortality, and overall mortality, respectively.

Results
A total of 560 patients were included. Higher CXR scores were associated with increased mortality; for every one-point increase in score, in-hospital mortality increased 10% (OR 1.10, CI 1.05–1.16, p < 0.001) and 60-day mortality increased by 12% (OR 1.12, CI 1.07–1.17, p < 0.001). CXR scores were also independently associated with both ICU length of stay (rate ratio 1.06, CI 1.04–1.07, p < 0.001) and duration of mechanical ventilation (rate ratio 1.05, CI 1.02–1.07, p < 0.001).

Conclusions
Higher values on a simple visual score of a patient’s CXR on admission to the medical ICU are associated with increased in-hospital mortality, 60-day mortality, overall mortality, length of ICU stay, and duration of mechanical ventilation.
Assessment of spinal cord motion as a new diagnostic MRI-parameter in cervical spinal canal stenosis: study protocol on a prospective longitudinal trial
Authors: Wolf Katharina , Krafft Axel J. , Egger Karl , Klingler Jan-Helge , Hubbe Ulrich , Reisert Marco , Hohenhaus Marc 
Published: October 2019

Abstract

Background
Increased spinal cord motion has been proven to be a relevant finding within spinal canal stenosis disclosed by phase-contrast MRI (PC-MRI). Adapted PC-MRI is a suitable and reliable method within the well deliberated setting. As the decision between conservative and operative treatment can be challenging in some cases, further diagnostic marker would facilitate the diagnostic process. We hypothesize that increased spinal cord motion will correlate to clinical course and functional impairment and will contribute as a new diagnostic marker.

Methods
A monocentric, prospective longitudinal observational trial on cervical spinal canal stenosis will be conducted at the University Medical Center Freiburg. Patients (n = 130) with relevant cervical spinal canal stenosis, being defined by at least contact to the spinal cord, will be included. Also, we will examine a control group of healthy volunteers (n = 20) as proof-of-principle. We will observe two openly assigned branches of participants undergoing conservative and surgical decompressive treatment (based on current German Guidelines) over a time course of 12 month, including a total of 4 visits. We will conduct a broad assessment of clinical parameters, standard scores and gradings, electrophysiological measurements, standard MRI, and adapted functional PC-MRI of spinal cord motion. Primary endpoint is the evaluation of an expected negative correlation of absolute spinal cord displacement to clinical impairment. Secondary endpoints are the evaluation of positive correlation of increased absolute spinal cord displacement to prolonged evoked potentials, prediction of clinical course by absolute spinal cord displacement, and demonstration of normalized spinal cord motion after decompressive surgery.

Discussion
With the use of adapted, non-invasive PC-MRI as a quantitative method for assessment of spinal cord motion, further objective diagnostic information can be gained, that might improve the therapeutic decision-making process. This study will offer the needed data in order to establish PC-MRI on spinal cord motion within the diagnostic work-up of patients suffering from spinal canal stenosis.

Trial registration
German Clinical Trials Register, ID: DRKS00012962, Register date 2018/01/17
Minimal invasive aortic valve replacement: associations of radiological assessments with procedure complexity
Authors: Boti Bruce R. , Hindori Vikash G. , Schade Emilio L. , Kougioumtzoglou Athina M. , Verbeek Eva C. , Driessen-Waaijer Annet , Cocchieri Riccardo , de Mol Bas A. J. M. , Planken Nils R. , Kaya Abdullah , Marquering Henk A. 
Published: October 2019

Abstract

Objectives
Limited aortic annulus exposure during minimal invasive aortic valve replacement (mini-AVR) proves to be challenging and contributes to procedure complexity, resulting in longer procedure times. New innovations like sutureless valves have been introduced to reduce procedure complexity. Additionally, preoperative imaging could also contribute to reducing procedure times. Therefore, we hypothesize that Computed Tomography (CT)-image based measurements are associated with mini-AVR complexity.

Methods
One hundred patients who underwent a mini-sternotomy and had a preoperative CT scan were included. With a CT-based mini-AVR planning tool, we measured access distance, access angle, annulus dimensions, and calcium volume. The associations of these measurements with cardiopulmonary bypass (CPB) time and aortic cross-clamp (AoX) time were assessed using univariable and multivariable regression models. In the multivariable models, these measurements were adjusted for age and suture technique.

Results
In the univariable regression models, calcium volume and annulus dimensions were associated with longer CPB and AoX time. After adjusting for age and suture technique, increasing calcium volume was still associated with longer CPB (adjusted β-coefficient 0.002, 95%-CI (0.005, 0.019), p-value = 0.002) and AoX time (adjusted β-coefficient 0.010, 95%-CI (0.004, 0.016), p-value = 0.002). However, after adjusting for these confounders, the association between annulus dimensions and procedure times lost statistical significance.

Conclusion
Increase in calcium volume are associated with longer CPB and AoX times, with age and sutureless valve implantation as independent confounders. In contrast to previous studies, access angle was not associated with procedure complexity.
Epigenetic down-regulation of the HIST1 locus predicts better prognosis in acute myeloid leukemia with NPM1 mutation
Authors: Garciaz Sylvain , N’guyen Dasi Lia , Finetti Pascal , Chevalier Christine , Vernerey Julien , Poplineau Mathilde , Platet Nadine , Audebert Stéphane , Pophillat Matthieu , Camoin Luc , Bertucci François , Calmels Boris , Récher Christian , Birnbaum Daniel , Chabannon Christian , Vey Norbert , Duprez Estelle 
Published: October 2019

AbstractBackgroundThe epigenetic machinery is frequently altered in acute myeloid leukemia. Focusing on cytogenetically normal (CN) AML, we previously described an abnormal H3K27me3 enrichment covering 70 kb on theHIST1cluster (6.p22) in CN-AML patient blasts. Here, we further investigate the molecular, functional, and prognosis significance of this epigenetic alteration named H3K27me3HIST1inNPM1-mutated (NPM1mut) CN-AML.ResultsWe found that three quarter of theNPM1mut CN-AML patients were H3K27me3HIST1high. H3K27me3HIST1highgroup of patients was associated with a favorable outcome independently of known molecular risk factors. In gene expression profiling, the H3K27me3HIST1highmark was associated with lower expression of the histone genesHIST1H1D,HIST1H2BG,HIST1H2AE, andHIST1H3Fand an upregulation of genes involved in myelomonocytic differentiation. Mass spectrometry analyses confirmed that the linker histone protein H1d, but not the other histone H1 subtypes, was downregulated in the H3K27me3HIST1highgroup of patients. H1d knockdown primed ATRA-mediated differentiation of OCI-AML3 and U937 AML cell lines, as assessed on CD11b/CD11c markers, morphological and gene expression analyses.ConclusionsOur data suggest thatNPM1mut AML prognosis depends on the epigenetic silencing of theHIST1cluster and that, among the H3K27me3 silenced histone genes,HIST1H1Dplays a role in AML blast differentiation.Graphical abstract