bluuebunny/crossref_metadata_2025 huggingface dataset:
MiRNA-12129 Suppresses Cell Proliferation and Block Cell Cycle Progression by Targeting SIRT1 in GASTRIC Cancer
Authors: Zhang Wei , Liao Kai , Liu Dongning
Published: June 2020

Gastric cancer is the most commonly occurring cancer with a rapidly increasing incidence rate worldwide. The underlying molecular mechanisms of gastric cancer require further investigation. MicroRNAs exhibit tissue sensitivity as tumor biomarkers that play a role by promoting tumor growth as oncogenes or tumor suppressor genes. We evaluated the effects of microRNA-12129 on gastric cancer and identified the underlying mechanisms of microRNA-12129. Quantitative real-time polymerase chain reaction was conducted to determine the expression levels of microRNA-12129 and sirtuin 1 in vivo and in vitro, and Western blot analysis was performed to detect sirtuin 1 at the protein level in gastric cancer cell lines. Cell proliferation and cell cycle progression were detected by Cell Counting Kit-8 assay and flow cytometry analysis, respectively. The potential targets of microRNA-12129 were predicted by bioinformatics analysis. The targets of microRNA-12129 were confirmed by luciferase reporter assay and rescue assay. We found that microRNA-12129 was downregulated in gastric cancer tissues and gastric cancer cell lines and was significantly associated with the prognosis of patients with gastric cancer. In addition, microRNA-12129 overexpression suppressed tumor cell proliferation and blocked cell cycle progression. Bioinformatics analysis and luciferase reporter assay suggested that sirtuin 1 was a target of microRNA-12129, and sirtuin 1 expression was negatively related to microRNA-12129. Restoration of sirtuin 1 partly reduced the inhibition of cell proliferation and cell cycle progression induced by microRNA-144. Our results collectively suggested that microRNA-12129 suppressed cell proliferation and cell cycle progression in gastric cancer by targeting sirtuin 1. These findings indicated that manipulation of microRNA-12129 expression could help develop a novel therapeutic strategy for gastric cancer.
Knockdown of Ubiquitin-Specific Protease 53 Enhances the Radiosensitivity of Human Cervical Squamous Cell Carcinoma by Regulating DNA Damage-Binding Protein 2
Authors: Zhou Qifen , Yao Xiongbo , Wu Chunlin , Chen Shaohua , Fan Dage
Published: June 2020

Background:

Cervical cancer ranks fourth in incidence and mortality among women. Ubiquitin-specific protein 53 binds to damage-specific DNA binding protein 2 and affects the biological properties of colon cancer. Damage-specific DNA binding protein is involved in nucleotide excision repair, which can repair DNA damage. However, the mechanism by which ubiquitin-specific protein 53 regulates the radiosensitivity of cervical cancer through damage-specific DNA binding protein remains unclear.

Methods:

Tissue samples from 40 patients with cervical squamous cell carcinoma who received radiotherapy were examined by immunohistochemistry to detect the expression of ubiquitin-specific protein 53, and clinical data were collected for statistical analysis. The cell cycle was detected by flow cytometry in Siha cells transfected with Si-USP53 and exposed to 8 Gy irradiation. Cell viability was determined by the CCK8 method in cells transfected with Si-USP53 and exposed to 0, 2, 4, 6, 8, or 10 Gy. The expression of damage-specific DNA binding protein, cyclin-dependent kinase 1, and cell cycle checkpoint kinase 2 was detected in cells transfected with Si-USP53.

Results:

The expression of ubiquitin-specific protein 53 in the tissues of patients with cervical squamous cell carcinoma was correlated with the sensitivity to radiotherapy. Knockdown of ubiquitin-specific protein 53 in Siha cells downregulated damage-specific DNA binding protein and caused G2/M cell cycle arrest and decreased the survival rate of cells in response to radiation.

Conclusion:

Ubiquitin-specific protein 53–induced cell cycle arrest and affected the radiotherapy sensitivity of tumors through damage-specific DNA binding protein.
Pilot Experience on the Use of S53P4 Bioactive Glass in the Surgical Management of Diabetic Foot Osteomyelitis
Authors: Iacopi Elisabetta , Pieruzzi Letizia , Goretti Chiara , Piaggesi Alberto
Published: June 2020

To test safety and efficacy of bioactive glass, a novel material used to replace bone, able to completely bond itself to the host tissues on patients treated for osteomyelitis (OM) complicating a diabetic foot (DF). We evaluated a group of patients consecutively admitted in our department between September and December 2018, who underwent surgical DF procedures for OM and in whom the use of bioactive glass could limit the demolition phase of surgical procedure. Patients were treated with bioactive glass S53P4 on top of standard treatment directly in operating room. The patients were weekly controlled for 6 months or until complete healing. During follow-up, we analyzed primarily healing rate and secondarily time of healing, need for further debridement procedures, recurrences, and adverse or hypersensitivity reactions to study treatment. Ten DF patients were enrolled (male/female 6/4; mean age 56 ± 11 years; mean duration of diabetes 10.5 ± 4.7 years, mean hemoglobin A1c 7.2 ± 0.9%). Patients underwent surgical procedure during which, after an accurate debridement, bioactive glass was applied. A healing rate of 80% in a mean time of 34 ± 2 days, with only 1 patient who needed a second surgical look, was observed. Neither recurrences nor adverse events during follow-up were observed in treated patients. This pilot experience demonstrated that bioactive glass can be considered a useful tool for the surgical treatment of DF-related OM.
Type 2 Diabetes Remission and Lifestyle Medicine: A Position Statement From the American College of Lifestyle Medicine
Authors: Kelly John , Karlsen Micaela , Steinke Gregory
Published: June 2020

Objectives. The present review represents the position of the American College of Lifestyle Medicine on type 2 diabetes (T2D) and remission treatment. Background. Research now reveals that sufficiently intensive lifestyle interventions can produce remission of T2D with similar success to bariatric surgery, but with substantially fewer untoward side effects. Methods. A literature review was conducted to examine lifestyle modifications targeting T2D remission, with most studies using a combination of blood glucose markers and treatment history. Results. There were notable differences in the dosing intensity of lifestyle interventions between therapeutic interventions and subtherapeutic interventions. Studies with therapeutic dosing typically used very low energy diets (600-1100 kcal/day) with a weighted mean remission rate of 49.4%, while studies with subtherapeutic dosing typically used more moderate caloric restrictions (reducing energy intake by 500-600 kcal/day) and the weighted mean remission rate was 6.9%. Conclusions. Remission should be the clinical goal in T2D treatment, using properly dosed intensive lifestyle interventions as a primary component of medical care for T2D patients.
Catholic education in Ireland and the United States: Teachers’ comparative perspectives
Authors: Kowalski Monica J , Tiernan Jonathan , McGraw Sean D
Published: June 2020

This article provides a comparative examination of teachers’ experiences of both participating in Catholic teacher education programmes and teaching within Catholic schools in the Republic of Ireland and the United States. This mixed-methods study consisted of surveys and interviews with 22 teachers who are graduates of both Irish and US teacher education programmes and have taught in Catholic schools in both countries. This distinct cohort of Irish Catholic educators reveals how faith and Catholic identity are experienced in two distinct education systems that share a common mission. The research underscores how context powerfully shapes the lived experience of teachers in both Catholic teacher education programmes and in Catholic schools, and it highlights implications for those responsible for Catholic teacher education programmes and also for the leaders of Catholic schools. The extent to which members of a school community explicitly identify and choose to embody the Catholic identity greatly shapes outcomes.
Design, Synthesis, and Cytotoxic Evaluation of Novel Lupane Triterpenoid Derived Hydroxamates
Authors: Tuyet Anh Dang Thi , Cuc Dinh Thi , Thuy Giang Le Nhat , Hien Nguyen Thi , Doan Vu Ngoc , Thanh Nguyen Ha , Tuyen Nguyen Van , Van Kiem Phan
Published: June 2020

A series of new hydroxamate derivatives of lupane triterpenoids has been designed and successfully synthesized. The synthesized compounds were evaluated for their in vitro antitumor activity using the 3-[4,5-dimethylthiazol-2-yl]−2,5-diphenyltetrazolium bromide-based assay against the human cancer cell lines KB and HepG2. Most of these derivatives possess at least moderate cytotoxic activity and the hydroxamate derivative compounds 3c, 3e, 7a, and 15b could be lead compounds for further optimization to develop novel anticancer agents.
In Vitro and In Vivo Effects of Holotoxin A1 From the Sea Cucumber Apostichopus japonicus During Ionizing Radiation
Authors: Malyarenko Olesya S. , Ivanushko Lyudmila A. , Chaikina Elena L. , Kusaykin Mikhail I. , Silchenko Alexandra S. , Avilov Sergey A. , Kalinin Vladimir I. , Ermakova Svetlana P.
Published: June 2020

Radiation therapy is one of the most important approaches to cancer therapy, but radiotoxicity to normal tissue is a serious limitation of this treatment. Compounds which are able to either sensitize cancer cells or protect normal cells to radiation are of great interest. The cytotoxicity of holotoxin A1 and the effects of radiation against DLD-1 and HT-29 cells were measured by MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assay. The effect of the combination of holotoxin A1 with X-ray on colony formation of cancer cells was determined by the soft agar assay. The effect of holotoxin A1 on the recovery of peripheral blood leukocyte number, mass, and cellularity of the lymphoid organs of irradiated mice, as well as on growth of murine Ehrlich solid carcinoma was studied. Holotoxin A1 enhanced the sensitivity of colorectal carcinoma cells to radiation in vitro. Injection of holotoxin A1 to mice led to an increase in the spleen endogenous colony number and peripheral blood leukocyte number, as well as the weight and cellularity of the lymphoid organs of the irradiated mice. Holotoxin A1 in combination with X-ray radiation effectively inhibited the growth of Ehrlich solid carcinoma in vivo. Holotoxin A1 is suggested to be a promising agent for improving the efficiency of radiotherapy.
Anti‐synthetase syndrome‐associated pulmonary veno‐occlusive disease
Authors: Kay Dana , Kadri Ferdous , Fitzpatrick Garrett , Alnuaimat Hassan , Reddy Raju , Ataya Ali
Published: June 2020

Pulmonary arterial hypertension has been reported with a prevalence of 7.9% in patients with anti‐synthetase syndrome; however, anti‐synthetase syndrome associated with pulmonary veno‐occlusive disease (PVOD) has never before been described in the literature. We present a novel case of anti‐synthetase syndrome‐associated PVOD in a patient who presented with hypoxic respiratory failure associated with right heart failure and was diagnosed with anti‐synthetase syndrome based on his autoimmune serology and pre‐capillary pulmonary hypertension on right heart catheterization. He was initiated on pulmonary arterial hypertension therapy, but with escalating dose of parenteral epoprostenol, experienced acute clinical worsening with chest imaging concerning for PVOD that was confirmed on autopsy. Anti‐synthetase syndrome can be associated with PVOD, and it should be suspected in patients who have evidence of pre‐capillary pulmonary hypertension and who deteriorate with the initiation of pulmonary hypertension‐specific therapy.
Expectations of technology use during meetings: An experimental test of manager policy, device use, and task-acknowledgment
Authors: Piercy Cameron W. , Underhill Greta R.
Published: June 2020

In organizational meetings, mobile media are commonly used to hold multiple simultaneous conversations (i.e., multicommunication). This experiment uses video vignettes to test how manager policy (no policy, pro-technology, anti-technology), device use (notepad, laptop, cell phone) and task-acknowledgment (no task-acknowledgment, task-acknowledgment) affect perceptions of meeting multicommunication behavior. US workers ( N = 243) who worked at least 30 hours per week and attended at least one weekly meeting rated relevant outcomes: expectancy violation, communicator evaluation, perceived competence, and meeting effectiveness. Results reveal manager policy and device use both affect multicommunication perceptions, with mobile phones generating the highest expectancy violation and lowest evaluation of the communicator and meeting effectiveness. Surprisingly, there was no effect for task-acknowledgment; however, a match between manager policy and task-acknowledgment affected evaluations. This paper unifies past evidence about multicommunication under the expectancy violations framework, extends theoretical understandings of mobile media use at work, and suggests practical implications for technology use in unfamiliar workplace situations.
Diagnostic challenge of a radiological mass post partial nephrectomy in a patient with a single functioning kidney: Surgicel® granuloma
Authors: Duffy Siobhan , Rodger Flora , Fraser Sioban , Oades Grenville
Published: June 2020

Here we describe a case review of a 61-year-old female who developed a Surgicel® granuloma following a partial nephrectomy for clear cell carcinoma in a single functioning kidney. We discuss the biodynamics of Surgicel®, the challenge of reaching the diagnosis and the implications of a Surgicel® granuloma for patients.

Level of evidence: Level 5
‘If you didn’t laugh, you’d cry’: Emotional labour, reflexivity and ethics-as-practice in a qualitative fieldwork context
Authors: McGowan William
Published: June 2020

This article takes Guillemin and Gillam’s distinction between ‘procedural ethics’ and ‘ethics in practice’ as a point of departure and return for reflecting critically on a recently completed doctoral research project about political violence and terrorism. It provides an overview of the study before offering some instructive vignettes to show how ethical decision-making processes engaged with ‘in the field’ were an extension of more everyday and mundane reasoning than we may typically associate with such quintessentially ‘sensitive research’. As the final section of this article argues, it is this everyday and mundane quality to ethical reasoning which is sometimes obscured in formal accounts of ‘reflexivity’. It is hoped that this article is useful for scholars interested in the ethics and emotional practices of qualitative inquiry, as well as those researching serious violence and bereavement.
Understanding pre-operative staging and surgical practice in advanced endometriosis: A survey of Canadian gynaecologists
Authors: Nica Andra , Liu Grace Y. , Selk Amanda , Kroft Jamie
Published: June 2020

Study objective:

To determine the pre-operative evaluation, surgical management and referral practices in patients with advanced stage endometriosis by Canadian gynaecologists.

Design:

A survey of obstetricians and gynaecologists.

Setting:

The survey was initiated and piloted at an academic centre by general gynaecologists and endometriosis specialists.

Intervention:

Electronically distributed to 733 individuals by the Society of Obstetricians and Gynaecologists of Canada. This included all members, irrespective of subspecialty and practice patterns.

Measurement:

Responses were collected using a web-based survey tool and analysed using Excel.

Results:

The response rate was 15.7% (115 respondents). Pre-operatively, 62.2% of respondents perform a transvaginal ultrasound on all of their patients, while magnetic resonance imaging is reserved for patients with physical exam findings suspicious for advanced endometriosis (26.7%) or in whom the surgeons suspect deep infiltrating endometriosis, bowel, bladder or uterosacral disease (54.4%). Most surgeons (81.4%) report encountering advanced disease that they did not suspect pre-operatively <10% of the time. Although 40% of respondents would refer their patients in whom they suspected deep infiltrating endometriosis, endometriomas, bowel, bladder or uterosacral ligament involvement to an endometriosis specialist prior to any attempted surgery, 54.4% would never refer without previously confirming the diagnosis at laparoscopy. In contrast, only 15% felt comfortable treating advanced endometriosis completely at time of laparoscopy (including deep infiltrating endometriosis, bladder and bowel disease). Post-operatively, 67.8% of respondents refer patients to an endometriosis specialist only if their disease was not appropriately treated surgically, while 23.3% do not refer any of their patients.

Conclusion:

Our study identified significant variability in the management of advanced endometriosis in Canada. Understanding these patterns will help us formulate a more universal investigation and management plan, which may improve the identification of patients pre-operatively with advanced stage endometriosis that could benefit from treatment by an endometriosis specialist.
Pediatric Thoracic Empyema—Outcomes of Intrapleural Thrombolytics: Ten Years of Experience
Authors: Baram Aram , Yaldo Fitoon
Published: June 2020

Introduction. Pediatric thoracic empyema is a special entity with increasing frequency. Consensus regarding the best management strategy is still evolving. We describe our single-center 10-year experience adopting intrapleural thrombolytics using tissue plasminogen activator as first-line treatment following failure of simple thoracostomy drainage techniques. Methods. Observational prospective study included all children from 1 day to 18 years admitted for parapneumonic effusion and treated with intrapleural thrombolytics. Results. From January 2008 to December 2018, 95 patients were treated by intrapleural thrombolytics for different stages of empyema thoracis. Number of thrombolytic doses required is 2.1 (range = 1-3), and mean amount of drainage is 1050 mL (range = 400-2500 mL). Mean total days of hospitalization is 7.3 days. Complete re-expansion was the primary outcome in 94 patients (98.9%). Conclusion. Intrapleural thrombolytics in complicated pediatric thoracic empyema results in excellent outcome and should be encouraged particularly in limited resource countries.
COVID-19 and Inequities in Oral Health Care for Older People: An Opportunity for Emerging Paradigms
Authors: León S. , Giacaman R.A.
Published: June 2020

Severe restrictions have been imposed in most countries for oral health care to the general population, allowing treatment only for emergencies, because of the generation of aerosols during clinical procedures and to ration personal protective equipment (PPE) during the pandemic. This article stresses the critical situation that affects oral health for older persons in the complex times of the COVID-19 pandemic. Older adults are at high risk for the viral infection, but neglected dental conditions may worsen their health, triggering infections that can lead to local and systemic complications, compromising general health. We propose that under current and possibly future scenarios, teledentistry and the minimal intervention dentistry approach may play a pivotal role in reshaping the profession. The already existent inequities in oral health care may be exacerbated due to the pandemic, especially in the developing world. More research along with a strong educational component in the dental curriculum must be emphasized. COVID-19 may be an opportunity to change canonical paradigms. The dental profession must reflect and take action to face future challenges.

Knowledge Transfer Statement:

This article provides an overview of the oral health situation imposed by COVID-19 and the minimal intervention alternatives to provide care to older people who are at risk and have reduced access to care.
The safety evaluation of phycocyanin-enriched Galdieria sulphuraria extract using 90-day toxicity study in rats and in vitro genotoxicity studies
Authors: Athané Axel , Demol Julien , Brosset-Vincent Sandra , Aguenou Corinne , Krisa Stéphanie , Courtois Arnaud , Griffiths Hywel , Cagnac Olivier
Published: June 2020

The microalgae Galdieria sulphuraria, which belong to the class of cyanidiophyceae, are thermostable at temperatures up to 55°C and have successfully been cultivated under controlled fermentation conditions to produce a protein-rich biomass from which a natural blue proteinaceous pigment, C-phycocyanin can be isolated. The C-phycocyanin has potential use as a colour additive and as a dietary supplement. This C-phycocyanin is resistant to acidic pH down to 2.75, in contrast to the one from Spirulina, which is already used as a colouring agent in agri-food applications. To further promote its use for industrial applications, we report, here, the results of a safety evaluation on a G. sulphuraria extract enriched to 33% C-phycocyanin. This was conducted in a 90-day repeated dose toxicity study in rats at doses from 250 to 4000 mg/kg body weight/day, in bacterial reversal mutation test at doses from 312.5 to 5000 µg/plate and in micronucleus assay at doses from 500 to 2000 µg/mL. Overall, our results indicated that the C-phycocyanin extract from G. sulphuraria did not exert any noteworthy adverse effect of toxicological significance in any of the system used for its safety evaluation, even if some minor changes were observed. According to the 90-day repeated dose toxicity study, no observed adverse effect level of 4000 mg/kg/day could be estimated. In conclusion, this study supports the safety of soluble fraction enriched with C-phycocyanin from G. sulphuraria for its use as food ingredient or supplement.
Investigating Pharmacists’ Views on Telepharmacy: Prioritizing Key Relationships, Barriers, and Benefits
Authors: Ameri Arefeh , Salmanizadeh Farzad , Keshvardoost Sareh , Bahaadinbeigy Kambiz
Published: June 2020

Background: Telepharmacy can help deliver pharmaceutical advice from an expert pharmacist to another party, such as a physician, inexperienced pharmacist, or pharmacy technician. In this study, we consider term “2-person discussions” as teleconsultation between expert pharmacists to each of the aforementioned persons. Objectives: This study has 2 aims: first to prioritize 2-person discussions between the parties involved in telepharmacy services when we have limited budget and time and would like to implement the best efficient telepharmacy system. Second to examine the barriers and benefits of implementing a telepharmacy. Methods: The research population included 40 pharmacists working in Kerman pharmacies (Iran). Their viewpoints were evaluated using a valid and reliable researcher-made questionnaire. The first part of the questionnaire focused on professional-demographic information, while the second part addressed the most important 2-person discussions and also asked about barriers to and benefits of implementing telepharmacy. Results: The findings indicate that the following 2-person discussions are priority for implementation: physician-pharmacist, pharmacist-hospital ward, and pharmacist-pharmacist. Payment and reimbursement issues and lack of access to information technology infrastructure were among the most important barriers. Efficient training about medicine usage, drug-drug interactions, and adverse effects was the most important benefit of telepharmacy. Conclusion: In this study, pharmacists’ first priority regarding who to involve in a 2-person telepharmacy consultation was to establish a long-distance connection between physicians and pharmacists. This finding indicates that the pharmacists were more interested in providing teleconsultation services to physicians and other pharmacists rather than communicating with pharmaceutical technicians.
Exposure model for European seismic risk assessment
Authors: Crowley Helen , Despotaki Venetia , Rodrigues Daniela , Silva Vitor , Toma-Danila Dragos , Riga Evi , Karatzetzou Anna , Fotopoulou Stavroula , Zugic Zeljko , Sousa Luis , Ozcebe Sevgi , Gamba Paolo
Published: June 2020

Building exposure and vulnerability models for seismic risk assessment have been the focus of a number of European projects in recent years, but there has never been a concerted effort among the research community to produce a uniform European risk model. The European Commission’s Horizon 2020 SERA project has a work package that is dedicated to that objective, through the development of an exposure model, an associated set of fragility/vulnerability models, and a database of socioeconomic indicators in order to calculate probabilistic integrated seismic risk at a European scale. This article provides details of the development of the first versions of the European exposure model that describe the distribution of the main residential, industrial and commercial building classes across all countries in Europe, as well as their occupants and replacement costs. The v0.1 of the European exposure model has been integrated within the Global Earthquake Model’s global exposure and risk maps. Preliminary analyses using the model show that almost 35% of the residential population in Europe is exposed to a 475-year return period peak ground acceleration (PGA) hazard of at least 0.1 g, thus highlighting the importance of European seismic risk modeling and mitigation.
Diagnosis of deep vein thrombosis of the upper extremity: a systematic review and meta-analysis of test accuracy
Authors: Patel Payal , Braun Cody , Patel Parth , Bhatt Meha , Begum Housne , Wiercioch Wojtek , Varghese Jamie , Wooldridge David , Alturkmani Hani J. , Thomas Merrill , Baig Mariam , Bahaj Waled , Khatib Rasha , Kehar Rohan , Ponnapureddy Rakesh , Sethi Anchal , Mustafa Ahmad , Lim Wendy , Le Gal Grégoire , Bates Shannon M. , Lang Eddy , Righini Marc , Husainat Nedaa M. , Kalot Mohamad A. , Al Jabiri Yazan Nayif , Nieuwlaat Robby , Schünemann Holger J. , Mustafa Reem A.
Published: June 2020

Upper extremity deep vein thrombosis (UEDVT) accounts for ≤10% of DVT and can be associated with morbidity and mortality. Accurate diagnosis and treatment are necessary for safe and effective patient management. We systematically reviewed the accuracy of D-dimer and duplex ultrasonography (US) for the evaluation of suspected first-episode UEDVT. We searched the Cochrane Central Register, OVID MEDLINE, EMBASE, and PubMed for eligible studies, reference lists of relevant reviews, registered trials, and relevant conference proceedings. We included prospective cross-sectional and cohort studies that evaluated test accuracy. Two investigators independently screened and collected data. The risk of bias was assessed using Quality Assessment of Diagnostic Accuracy Studies 2 and certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation framework. We pooled estimates of sensitivity and specificity. The review included 9 studies. The pooled estimates for D-dimer sensitivity and specificity were 0.96 (95% confidence interval [CI], 0.87-0.99) and 0.47 (95% CI, 0.43-0.52), respectively. The pooled estimates for duplex US sensitivity and specificity were 0.87 (95% CI, 0.73-0.94) and 0.85 (95% CI, 0.72-0.93), respectively. Certainty of evidence was moderate. In this review, we summarized the test accuracy (sensitivity and specificity) of D-dimer and duplex US for this indication. The sensitivity and specificity of the tests found in the present review should be considered in the context of whether they are used alone or in combination, which is dependent on the prevalence of disease in the population, the clinical setting in which the patient is being evaluated, cost, potential harms, and patient outcomes. This study was registered at PROSPERO as Systematic Review Registration Number CRD42018098488.
Transient antibody targeting of CD45RC inhibits the development of graft-versus-host disease
Authors: Boucault Laetitia , Lopez Robles Maria-Dolores , Thiolat Allan , Bézie Séverine , Schmueck-Henneresse Michael , Braudeau Cécile , Vimond Nadège , Freuchet Antoine , Autrusseau Elodie , Charlotte Frédéric , Redjoul Rabah , Beckerich Florence , Leclerc Mathieu , Piaggio Eliane , Josien Regis , Volk Hans-Dieter , Maury Sébastien , Cohen José L. , Anegon Ignacio , Guillonneau Carole
Published: June 2020

Allogeneic bone marrow transplantation (BMT) is a widely spread treatment of many hematological diseases, but its most important side effect is graft-versus-host disease (GVHD). Despite the development of new therapies, acute GVHD (aGVHD) occurs in 30% to 50% of allogeneic BMT and is characterized by the generation of effector T (Teff) cells with production of inflammatory cytokines. We previously demonstrated that a short anti-CD45RC monoclonal antibody (mAb) treatment in a heart allograft rat model transiently decreased CD45RChigh Teff cells and increased regulatory T cell (Treg) number and function allowing long-term donor-specific tolerance. Here, we demonstrated in rat and mouse allogeneic GVHD, as well as in xenogeneic GVHD mediated by human T cells in NSG mice, that both ex vivo depletion of CD45RChigh T cells and in vivo treatment with short-course anti-CD45RC mAbs inhibited aGVHD. In the rat model, we demonstrated that long surviving animals treated with anti-CD45RC mAbs were fully engrafted with donor cells and developed a donor-specific tolerance. Finally, we validated the rejection of a human tumor in NSG mice infused with human cells and treated with anti-CD45RC mAbs. The anti-human CD45RC mAbs showed a favorable safety profile because it did not abolish human memory antiviral immune responses, nor trigger cytokine release in in vitro assays. Altogether, our results show the potential of a prophylactic treatment with anti-human CD45RC mAbs in combination with rapamycin as a new therapy to treat aGVHD without abolishing the antitumor effect.
Risks for cold frequency vary by sex: role of asthma, age, TLR7 and leukocyte subsets
Authors: Murray Liisa M. , Yerkovich Stephanie T. , Ferreira Manuel A. , Upham John W.
Published: June 2020

Viral respiratory infections are usually benign but can trigger asthma exacerbations. The factors associated with upper respiratory tract infection (cold) frequency are not fully understood, nor is it clear whether such factors differ between women and men.

To determine which immunological and clinical variables associate with the frequency of self-reported respiratory infections (colds), 150 asthma cases and 151 controls were recruited. Associations between antiviral immune response variables: toll-like receptor (TLR)7/8 gene expression, plasmacytoid dendritic cell (pDC) numbers and interferon-α, tumour necrosis factor and interleukin-12 production, and asthma were then examined that might explain cold frequency.

People with asthma cases reported more colds per year (median 3versus2; p<0.001) and had lower baseline TLR7 gene expression (odds ratio 0.12; p=0.02) than controls. Associations between many variables and cold frequency differed between women and men. In women, high blood neutrophil counts (β=0.096, p=0.002), and younger age (β=−0.017, p<0.001), but not exposure to children, were independently associated with more frequent colds. In men, low TLR7 expression (β=−0.96, p=0.041) and high CLEC4C gene expression (a marker of pDC; β=0.88, p=0.008) were independently associated with more frequent colds. Poor asthma symptom control was independently associated with reduced TLR8 gene expression (β=−1.4, p=0.036) and high body mass index (β=0.041, p=0.004).

Asthma, age and markers of inflammation and antiviral immunity in peripheral blood are associated with frequent colds. Interestingly, the variables associated with cold frequency differed between women and men.
Variability in airway inflammation, symptoms, lung function and reliever use in asthma: anti-inflammatory reliever hypothesis and STIFLE study design
Authors: Harrison Tim , Pavord Ian D. , Chalmers James D. , Whelan Glenn , Fagerås Malin , Rutgersson Annika , Belton Laura , Siddiqui Shahid , Gustafson Per
Published: June 2020

Asthma is a chronic inflammatory airway disease. Increase in airway inflammation is hypothesised to contribute to worsening of asthma symptoms and deterioration in lung function, resulting in the use of reliever medication. Short-acting β2-agonists only treat the symptoms, whereas an anti-inflammatory reliever is believed to treat both symptoms and the underlying inflammation, thereby arresting the progression to an exacerbation. As-needed budesonide/formoterol as an anti-inflammatory reliever reduces the risk of severe exacerbations. However, supporting mechanistic evidence has not yet been described, specifically the temporal dynamics of parameters including airway inflammation, over time and during asthma worsening.

The STIFLE study aims to characterise daily variability in airway inflammation, symptoms, lung function and reliever use in people with asthma. This phase IV, open-label, parallel-group, multicentre, exploratory study will enrol 60–80 adult patients with asthma receiving low- or medium-dose inhaled corticosteroids/long-acting β2-agonists (EudraCT identifier number 2018-003467-64). Participants will be randomised 1:1 to either as-needed budesonide/formoterol dry-powder inhaler or salbutamol reliever for 24 weeks, in addition to their maintenance therapy. Daily data will be captured for fractional exhaled nitric oxide, spirometry, asthma symptoms and medication use using devices connected to a smartphoneviathe STIFLE application. STIFLE will thereby enable not only characterisation of the variability of airway inflammation and clinical outcomes in relation to asthma worsening, but also elucidate the effect of as-needed budesonide/formoterol on airway inflammation against a background of daily maintenance therapy.
Integrated Modelling of Microstructure Evolution and Mechanical Properties Prediction for Q&P Hot Stamping Process of Ultra-High Strength Steel
Authors: Chen Yang , Zhang Huizhen , Tang Johnston Jackie , Han Xianhong , Cui Zhenshan
Published: June 2020

High strength steel products with good ductility can be produced via Q&P hot stamping process, while the phase transformation of the process is more complicated than common hot stamping since two-step quenching and one-step carbon partitioning processes are involved. In this study, an integrated model of microstructure evolution relating to Q&P hot stamping was presented with a persuasively predicted results of mechanical properties. The transformation of diffusional phase and non-diffusional phase, including original austenite grain size individually, were considered, as well as the carbon partitioning process which affects the secondary martensite transformation temperature and the subsequent phase transformations. Afterwards, the mechanical properties including hardness, strength, and elongation were calculated through a series of theoretical and empirical models in accordance with phase contents. Especially, a modified elongation prediction model was generated ultimately with higher accuracy than the existed Mileiko’s model. In the end, the unified model was applied to simulate the Q&P hot stamping process of a U-cup part based on the finite element software LS-DYNA, where the calculated outputs were coincident with the measured consequences.
Effect of desk materials on affective states and cognitive performance
Authors: Lipovac Dean , Podrekar Nastja , Burnard Michael D. , Šarabon Nejc
Published: June 2020

Visual and tactile properties of materials can influence human emotional and cognitive functioning. Existing studies indicate that exposure to wood may lead to more favourable outcomes than contact with other common materials, but evidence is limited. We measured affective states and cognitive performance in 16 participants before and after each spent 15 min at 10 desks with differing top surfaces. Desk surfaces were made of untreated, oiled, or lacquered spruce or oak solid wood, laminated or oak-veneered particleboard, glass, and mineral-filled thermoplastic composite. The results indicate that cognitive performance and affective states of participants did not differ between the desk surfaces. It appears that exposure to a relatively small wooden surface does not significantly influence affective and cognitive outcomes. Incorporating larger amounts of wood coverage and a more demanding cognitive task would probably increase the chances of capturing the potential effects of wood exposure on human affective states and cognitive performance.
Vehicle energy savings by optimizing road speed-sectioning
Authors: Coiret Alex , Deljanin Emir , Vandanjon Pierre-Olivier
Published: June 2020

In a context of decreasing resources and of climate change, lowering road vehicles consumption is a key point to meet CO2reduction requirements. In addition to car technological advances, eco-driving is part of the solution but the road infrastructure should ensure its development. This work aims to demonstrate that road energy demand and associated pollutant emissions can be reduced by working out minor optimization of road infrastructure itself. For this to happen, a simple eco-driving potential criterion is built upon infrastructure parameters such as slopes and sight distances. This criterion aims to detect Misplaced Speed-sectioning Positions (MSP) with regard to the Starting Point of Deceleration (SPD); with speed-sectioning being the succession of speed changes along a given route. An enhanced energy waste formulation is then developed to quantify the vehicles energy waste due to misplaced road-signs. Thirdly, a traffic simulation constitutes a framework for energy evaluation; considering a full flow of vehicles, based on real traffic data, and by modeling several driver behaviors. Simulation results show that a significant fuel reduction of up to 5.5% can be achieved locally, simply by moving a road sign, for rural areas and without degrading road safety.
An improved clear cell renal cell carcinoma stage prediction model based on gene sets
Authors: Li Fangjun , Yang Mu , Li Yunhe , Zhang Mingqiang , Wang Wenjuan , Yuan Dongfeng , Tang Dongqi
Published: June 2020

Background

Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal cell carcinoma and accounts for cancer-related deaths. Survival rates are very low when the tumor is discovered in the late-stage. Thus, developing an efficient strategy to stratify patients by the stage of the cancer and inner mechanisms that drive the development and progression of cancers is critical in early prevention and treatment.

Results

In this study, we developed new strategies to extract important gene features and trained machine learning-based classifiers to predict stages of ccRCC samples. The novelty of our approach is that (i) We improved the feature preprocessing procedure by binning and coding, and increased the stability of data and robustness of the classification model. (ii) We proposed a joint gene selection algorithm by combining the Fast-Correlation-Based Filter (FCBF) search with the information value, the linear correlation coefficient, and variance inflation factor, and removed irrelevant/redundant features. Then the logistic regression-based feature selection method was used to determine influencing factors. (iii) Classification models were developed using machine learning algorithms. This method is evaluated on RNA expression value of clear cell renal cell carcinoma derived from The Cancer Genome Atlas (TCGA). The results showed that the result on the testing set (accuracy of 81.15% and AUC 0.86) outperformed state-of-the-art models (accuracy of 72.64% and AUC 0.81) and a gene set FJL-set was developed, which contained 23 genes, far less than 64. Furthermore, a gene function analysis was used to explore molecular mechanisms that might affect cancer development.

Conclusions

The results suggested that our model can extract more prognostic information, and is worthy of further investigation and validation in order to understand the progression mechanism.
Effects of CO2 limitation on the metabolism of Pseudoclostridium thermosuccinogenes
Authors: Koendjbiharie Jeroen Girwar , Post Wilbert Berend , Palmer Martí Munar , van Kranenburg Richard
Published: June 2020

Background

Bio-based succinic acid holds promise as a sustainable platform chemical. Its production through microbial fermentation concurs with the fixation of CO2, through the carboxylation of phosphoenolpyruvate. Here, we studied the effect of the available CO2 on the metabolism of Pseudoclostridium thermosuccinogenes, the only known succinate producing thermophile. Batch cultivations in bioreactors sparged with 1 and 20% CO2 were conducted that allowed us to carefully study the effect of CO2 limitation.

Results

Formate yield was greatly reduced at low CO2 concentrations, signifying a switch from pyruvate formate lyase (PFL) to pyruvate:ferredoxin oxidoreductase (PFOR) for acetyl-CoA formation. The corresponding increase in endogenous CO2 production (by PFOR) enabled succinic acid production to be largely maintained as its yield was reduced by only 26%, thus also maintaining the concomitant NADH re-oxidation, essential for regenerating NAD+ for glycolysis. Acetate yield was slightly reduced as well, while that of lactate was slightly increased. CO2 limitation also prompted the formation of significant amounts of ethanol, which is only marginally produced during CO2 excess. Altogether, the changes in fermentation product yields result in increased ferredoxin and NAD+ reduction, and increased NADPH oxidation during CO2 limitation, which must be linked to reshuffled (trans) hydrogenation mechanisms of those cofactors, in order to keep them balanced. RNA sequencing, to investigate transcriptional effects of CO2 limitation, yielded only ambiguous results regarding the known (trans) hydrogenation mechanisms.

Conclusions

The results hinted at a decreased NAD+/NADH ratio, which could ultimately be responsible for the stress observed during CO2 limitation. Clear overexpression of an alcohol dehydrogenase (adhE) was observed, which may explain the increased ethanol production, while no changes were seen for PFL and PFOR expression that could explain the anticipated switch based on the fermentation results.
NaCl improves reproduction by enhancing starch accumulation in the ovules of the euhalophyte Suaeda salsa
Authors: Guo Jianrong , Du Ming , Lu Chaoxia , Wang Baoshan
Published: June 2020

Background

Halophytes show optimal reproduction under high-salinity conditions. However, the role of NaCl in reproduction and its possible mechanisms in the euhalophyte Suaeda salsa remain to be elucidated.

Results

We performed transcript profiling of S. salsa flowers and measured starch accumulation in ovules, sugar contents in flowers, and photosynthetic parameters in the leaves of plants supplied with 0 and 200 mM NaCl. Starch accumulation in ovules, sugar contents in flowers and ovules, and net photosynthetic rate and photochemical efficiency in leaves were significantly higher in NaCl-treated plants vs. the control. We identified 14,348 differentially expressed genes in flowers of NaCl-treated vs. control plants. Many of these genes were predicted to be associated with photosynthesis, carbon utilization, and sugar and starch metabolism. These genes are crucial for maintaining photosystem structure, regulating electron transport, and improving photosynthetic efficiency in NaCl-treated plants. In addition, genes encoding fructokinase and sucrose phosphate synthase were upregulated in flowers of NaCl-treated plants.

Conclusions

The higher starch and sugar contents in the ovules and flowers of S. salsa in response to NaCl treatment are likely due to the upregulation of genes involved in photosynthesis and carbohydrate metabolism, which increase photosynthetic efficiency and accumulation of photosynthetic products under these conditions.
Significant association between rs28362491 polymorphism in NF-κB1 gene and coronary artery disease: a meta-analysis
Authors: Wang Yanwei , Wu Bianwen , Zhang Muqing , Miao Huawei , Sun Jiaan
Published: June 2020

Background

The association of rs28362491 polymorphism in NF-κB1 gene and coronary artery disease (CAD) risk was reported in several studies with inconsistent outcomes. This study aimed to comprehensively collect and synthesize the existing evidence to appraise whether rs28362491 was correlated to CAD susceptibility.

Methods

Databases of Web of Science, EMBASE, PubMed, Wanfang, and CNKI were retrieved from inception to August 1, 2019 without any restriction on language. The strengths of association between rs28362491 polymorphism and CAD were presented as odds ratios (ORs) and 95% confidence intervals (CIs).

Results

Thirteen case-control studies with 17 individual cohorts containing 9378 cases and 10,738 controls were incorporated into this meta-analysis. The findings indicated that rs28362491 polymorphism was significantly correlated to CAD risk in five genetic models: D vs. I, OR = 1.16, 95%CI 1.11–1.21, P<0.01; DD vs. II, OR = 1.37, 95%CI 1.25–1.49, P<0.01; DI vs. II, OR = 1.11, 95%CI 1.05–1.18, P<0.01; DD + DI vs. II, OR = 1.17, 95%CI 1.11–1.24, P<0.01; DD vs. DI + II, OR = 1.29, 95%CI 1.15–1.43, P<0.01. After stratification by ethnicity and gender, significant association still existed between rs28362491 and CAD, especially in the dominant model.

Conclusions

The findings suggest that the mutant D allele in rs28362491 locus may increase the risk of CAD, and carriers of D allele appear to be more susceptible to CAD.
Evidence for deprescription in primary care through an umbrella review
Authors: Olry de Labry Lima Antonio , Marcos Marcos Jorge , Marquina Marquez Alfonso , González Vera María de los Ángeles , Matas Hoces Antonio , Bermúdez Tamayo Clara
Published: June 2020

Background

There is a high prevalence of potentially inappropriate prescriptions in primary care. This is associated with more frequent adverse events, lower quality of life and more frequent visits to hospital accident & emergency departments. The aim of the present study is to summarise available evidence on the effectiveness of deprescription interventions in primary care, and to describe the barriers and enablers of the process from the point of view of patients and healthcare professionals.

Methods

We designed an umbrella review which includes nine systematic reviews. More than 50% of included studies were performed with adults in primary care. Two reviewers independently performed data extraction and analysis.

Results

In considering studies of the effectiveness of interventions, it can be observed that the educational component of deprescription procedures is a key factor, whilst procedures tailored towards the patient’s situation offer better results. With regards to studies involving healthcare professionals, the main explored areas were the balance between risks and benefits, and the need to improve communication with patients as well as other colleagues involved in patient care. Amongst the identified barriers we found lack of time, inability to access all information, being stuck in a routine, resistance to change and a lack of willingness to question the prescription decisions made by healthcare colleagues. With regards to patients, it is clear that they have worries and doubts. In order to overcome these issues, a good relationship with healthcare professionals and receipt of their support is required during the process.

Conclusions

Optimizing medication through targeted deprescribing is an important part of managing chronic conditions, avoiding adverse effects and improving outcomes. The majority of deprescription interventions in primary care are effective. Good communication between healthcare professionals is a key element for success in the deprescription process.