bluuebunny/crossref_metadata_2025 huggingface dataset:
Preventive maintenance model based on the renewal-geometric process
Authors: Niu Caiyun , Jiang Jiang , Ge Bingfeng , Chen Yingwu
Published: June 2020

Renewal-geometric process is used to describe such a non-homogeneous deteriorating process that a system will deteriorate after several consecutive repairs, not after each repair described by the geometric process. In the maintenance domain, the effect of corrective maintenance after failure is generally not repairable as new (e.g. geometrically deteriorating). Preventive maintenance is critical before a system failure, due to economic losses and security threats caused by a sudden shutdown. Therefore, this article assumes that a system is geometrically deteriorating after corrective maintenance, wherein preventive maintenances sequence in the same repair period form a renewal process since it can restore the system to the initial state of the period. Furthermore, a binary policy [Formula: see text] is utilized to minimize the long-run average cost rate, where [Formula: see text] represents the number corrective maintenances and [Formula: see text] denotes the time interval between two consecutive preventive maintenances. In particular, pseudo-age replacement model represents a special case of [Formula: see text], which is considered as a generalization of the traditional age-based replacement model. Subsequently, the optimal policy [Formula: see text] can be verified in theory and an asymptotic optimal policy [Formula: see text] can be obtained based on a heuristic grid search. Finally, numerical examples verify the effectiveness of this proposed model and show that implementation of preventive maintenance for some repairable systems is superior to no preventive maintenance in both economic and reliability aspects.
Probabilistic analysis of tunnel face stability considering spatially variable undrained shear strength with linearly increasing mean trend
Authors: Cheng Hongzhan
Published: June 2020

The inherent spatial variability of soil properties has been considered as one of the main sources of uncertainties in geotechnical problems. The need for probabilistic analysis of the tunnel face stability that takes into account the variability of soil properties has been acknowledged. This article employed a probabilistic-based method, called random finite difference method, for evaluating the stability of tunnel face under the influence of the variability of undrained shear strength in clays. The two-dimensional spatial variation in soil undrained shear strength is modeled by random fields, which are discretized by the Covariance Matrix Decomposition method. The procedure for random finite difference method is presented. An illustrative example is employed to investigate the effect of soil variability. Particular attention has been paid to the situation that undrained shear strength increases with depth. The results demonstrate that ignoring the variability of undrained shear strength will result in overestimates of the tunnel face stability if the support pressure of the tunnel face exceeds the deterministic value, especially for higher coefficient of variation of soil undrained shear strength. Minor differences in the failure mechanism are observed in comparison to the deterministic case, considering only the global failure of the tunnel face is observed. In addition, ignoring the increase of undrained shear strength with depth will lead to conservative designs. The random finite difference method can provide a practical tool for evaluating the stability of a tunnel face in variable soils.
The cost-saving switch from inhaled corticosteroid-containing treatments to dual bronchodilation: a two-country projection of epidemiological and economic burden in chronic obstructive pulmonary disease
Authors: Souliotis Kyriakos , Silva Miguel Luís , Hillas Georgios , Borges Margarida , Papageorgiou Giannis , Viana Diogo , Malhadeiro Joao , Soulard Stéphane
Published: June 2020

Purpose:

The Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2018 recommendations support maintenance treatment with long-acting bronchodilators in most symptomatic patients with chronic obstructive pulmonary disease (COPD). While restricting the overuse of inhaled corticosteroids (ICS) may influence healthcare utilization required to treat inadvertent respiratory (exacerbations and pneumonia) and diabetes-related events, it may also change the total medication cost. This analysis was performed to estimate the 5-year budget impact of switching from ICS-containing treatment combinations to dual bronchodilation, in line with the recommendations.

Methods:

The model quantified the budget impact of treatment and healthcare resource utilization when COPD patients were anticipated to switch from ICS-containing treatments to dual bronchodilation. Three switch scenarios were calculated with increasing proportions of patients on dual long-acting bronchodilators, to the detriment of ICS-containing double and triple combinations. Clinical and cost input data were based on results from clinical trials and Greek and Portuguese healthcare cost databases.

Results:

Healthcare resource use to manage exacerbations, pneumonia and diabetes-related events were projected to increase between 2019 and 2023 in parallel with the growing COPD patient population and associated costs were estimated at 52–57% of the total disease cost in the Greek and Portuguese base case scenarios. Total cost savings between 21 and 112 million EUR were projected when the proportion of patients on double and triple ICS-containing treatments was gradually reduced to 50% in scenario A, 20% in scenario B and 7% in scenario C. Sensitivity analyses showed that none of the model assumptions had a major impact on the projected savings.

Conclusion:

The alignment of COPD treatment with current recommendations may bring clinical benefits to patients, without substantial cost increases and even cost savings for payers. The reviews of this paper are available via the supplemental material section.
The average peak time and intensity of seasonal influenza may vary by age: a study of laboratory confirmed influenza
Authors: Tharu Bhikhari P
Published: June 2020

Background:

Seasonal influenza (SI) is an acute respiratory illness that exerts a severe impact on human life year-round. Yet, very few studies have been conducted to investigate its peak timing for different age groups.

Objective:

To evaluate the average peak calendar time and intensity for the incidence of SI for different age groups.

Methods:

The study uses laboratory-confirmed Influenza data from the Centers for Disease Control and Prevention (CDC) of the USA with age groups 2, 11, 34, 57 and 65 years during 2009–2018 for the analysis. A non-parametric method of estimation of a circular probability distribution called likelihood cross-validation method has been utilised.

Results:

The average peak date of incidence for age groups 2 and 11 is around the last week of December. However, the date shifts to the last week of January to the first week of February for other groups. Age groups 65 and 2 years experienced the most severe impact among all.

Discussion:

The average peak time for SI incidence is between the last week of December to January with a single peak time for every age group. However, the incidence seems to develop an additional moderate peak time for age group 65.
Political Agenda Setting in the Hybrid Media System: Why Legacy Media Still Matter a Great Deal
Authors: Langer Ana Ines , Gruber Johannes B.
Published: June 2020

This article examines the roles of the media in the process of political agenda setting. There is a long tradition of studies on this topic, but they have mostly focused on legacy news media, thus overlooking the role of other actors and the complex hybrid dynamics that characterize contemporary political communication. In contrast, through an in-depth case study using mixed-methods and multiplatform data, this article provides a detailed analysis of the roles and interactions between different types of media and how they were used by political and advocacy elites. It explores what happened in the different parts of the system, and thus the paths to attention that led to setting this issue in the political and media agendas. The analysis of the case, a partial policy reversal in the United Kingdom provoked by an immigration scandal known as the “Windrush scandal” reveals that the issue was pushed into the agenda by a campaign assemblage of investigative journalism, political and advocacy elites, and digitally enabled leaders. The legacy news media came late but were crucial. They greatly amplified the salience of the issue and, once in “storm mode,” they were key for sustaining attention and pressure, eventually compelling the government to respond. It shows that they often remain at the core of the “national conversation” and certainly in the eye of a media storm. In the contemporary context, characterized by fierce battles for attention, shortening attention spans and fractured audiences, this is key and has important implications for agenda setting and beyond.
Prevalence and factors associated with adherence to anti-hypertensives among adults with hypertension in a developed Asian community: A cross-sectional study
Authors: Kang Gary Chun Yun , Koh Eileen Yi Ling , Tan Ngiap Chuan
Published: June 2020

Introduction:

Poor adherence to anti-hypertensive medications (AHM) results in hypertension treatment failure. Understanding and addressing the factors associated with adherence to AHM may potentially improve health outcomes. This study aimed to assess the prevalence and factors associated with patients’ adherence to AHM in a developed Asian community.

Methods:

An assistant-administered questionnaire survey was conducted on multi-ethnic Asian adults aged 31–80 years with essential hypertension based on their electronic health records (EHR) at a public primary-care clinic. Data on their demographic characteristics, clinical measurements of blood pressure and body mass index, co-morbidities and prescriptions from the EHR, along with the Medication Adherence Report Scale-5 scores were collated, audited and analysed. A MARS-5 score of <25 indicated poor adherence. Logistic regression was used to identify factors associated with adherence to AHM.

Results:

Data of 395 patients were analysed. Of these, 179 (45.3%) had poor adherence to at least one AHM. Bivariate analysis showed that poor adherence was significantly associated with lower mean age (59 years old vs. 63 years old), higher mean clinic diastolic blood pressure (76 mmHg vs. 73 mmHg) and higher mean weight (70.4 kg vs. 67.4 kg). Logistic regression showed that patients with no co-morbidities (such as diabetes mellitus, dyslipidaemia, stroke and ischaemic heart disease) had better medication adherence (MA; odds ratio=1.98; 95% confidence interval 1.14–3.45; p=0.02). There was no significant MA difference between the classes, dose frequency and number of AHM.

Conclusion:

Almost half of the patients had poor adherence to at least one AHM. Co-morbidity significantly influenced their MA. Attention should be directed to patients with co-morbidities to assess their AHM adherence.
Bone regeneration capacities of alveolar bone mesenchymal stem cells sheet in rabbit calvarial bone defect
Authors: Liu Yanan , Wang Haifeng , Dou Huixin , Tian Bin , Li Le , Jin Luyuan , Zhang Zhenting , Hu Lei
Published: June 2020

Mesenchymal stem cells sheets have been verified as a promising non-scaffold strategy for bone regeneration. Alveolar bone marrow mesenchymal stem cells, derived from neural crest, have the character of easily obtained and strong multi-differential potential. However, the bone regenerative features of alveolar bone marrow mesenchymal stem cells sheets in the craniofacial region remain unclear. The purpose of the present study was to compare the osteogenic differentiation and bone defect repairment characteristics of bone marrow mesenchymal stem cells sheets derived from alveolar bone (alveolar bone marrow mesenchymal stem cells) and iliac bone (Lon-bone marrow mesenchymal stem cells) in vitro and in vivo. Histology character, osteogenic differentiation, and osteogenic gene expression of human alveolar bone marrow mesenchymal stem cells and Lon-bone marrow mesenchymal stem cells were compared in vitro. The cell sheets were implanted in rabbit calvarial defects to evaluate tissue regeneration characteristics. Integrated bioinformatics analysis was used to reveal the specific gene and pathways expression profile of alveolar bone marrow mesenchymal stem cells. Our results showed that alveolar bone marrow mesenchymal stem cells had higher osteogenic differentiation than Lon-bone marrow mesenchymal stem cells. Although no obvious differences were found in the histological structure, fibronectin and integrin β1 expression between them, alveolar-bone marrow mesenchymal stem cells sheet exhibited higher mineral deposition and expression levels of osteogenic marker genes. After being transplanted in the rabbit calvarial defects area, the results showed that greater bone volume and trabecular thickness regeneration were found in bone marrow mesenchymal stem cells sheet group compared to Lon-bone marrow mesenchymal stem cells group at both 4 weeks and 8 weeks. Finally, datasets of bone marrow mesenchymal stem cells versus Lon-bone marrow mesenchymal stem cells, and periodontal ligament mesenchymal stem cells (another neural crest derived mesenchymal stem cells) versus umbilical cord mesenchymal stem cells were analyzed. Total 71 differential genes were identified by overlap between the 2 datasets. Homeobox genes, such as LHX8, MKX, PAX9, MSX, and HOX, were identified as the most significantly changed and would be potential specific genes in neural crest mesenchymal stem cells. In conclusion, the Al-bone marrow mesenchymal stem cells sheet-based tissue regeneration appears to be a promising strategy for craniofacial defect repair in future clinical applications.
Impact of timing of intraaortic balloon counterpulsation on mortality in cardiogenic shock – a subanalysis of the IABP-SHOCK II trial
Authors: Fuernau Georg , Ledwoch Jakob , Desch Steffen , Eitel Ingo , Thelemann Nathalie , Jung Christian , de Waha-Thiele Suzanne , Pöss Janine , Feistritzer Hans-Josef , Freund Anne , Schneider Steffen , Ouarrak Taoufik , Werdan Karl , Zeymer Uwe , Thiele Holger
Published: June 2020

Background

Conflicting results exist on whether initiation of intraaortic balloon pumping (IABP) before percutaneous coronary intervention (PCI) has an impact on outcome in this setting. Our aim was to assess the outcome of patients undergoing IABP insertion before versus after primary PCI in acute myocardial infarction complicated by cardiogenic shock.

Methods

The IABP-SHOCK II-trial randomized 600 patients with acute myocardial infarction and cardiogenic shock to IABP-support versus control. We analysed the outcome of patients randomized to the intervention group regarding timing of IABP implantation before or after PCI.

Results

Of 600 patients included in the IABP-SHOCK II trial, 301 were randomized to IABP-support. We analysed the 275 (91%) patients of this group undergoing primary PCI as revascularization strategy surviving the initial procedure. IABP insertion was performed before PCI in 33 (12%) and after PCI in 242 (88%) patients. There were no differences in baseline arterial lactate (p = 0.70), Simplified Acute Physiology Score-II-score (p = 0.60) and other relevant baseline characteristics. No differences were observed for short- and long-term mortality (pre vs. post 30-day mortality: 36% vs. 37%, odds ratio 0.99, 95% confidence interval (CI) 0.47–2.12, p = 0.99; one-year mortality: 56% vs. 48%, hazard ratio 1.08, 95% CI 0.65–1.80, p = 0.76; six-year-mortality: 64% vs. 65%, hazard ratio 1.00, 95% CI 0.63–1.60, p = 0.99). In multivariable Cox regression analysis timing of IABP-implantation was no predictor for long-term outcome (hazard ratio 1.08, 95% CI 0.66–1.78, p = 0.75).

Conclusions

Timing of IABP-implantation pre or post primary PCI had no impact on outcome in patients with acute myocardial infarction complicated by cardiogenic shock.
Preventing SARS-CoV-2 infection by blocking a tissue serine protease
Authors: Jankousky Katherine C. , Schultz Jonathan , Windham Samuel , Henao-Martínez Andrés F. , Franco-Paredes Carlos , Shapiro Leland
Published: June 2020

Currently, there are no proven pharmacologic interventions to reduce the clinical impact and prevent complications of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, the cause of the ongoing Coronavirus Disease of 2019 (COVID-19) pandemic. Selecting specific pharmacological targets for the treatment of viral pathogens has traditionally relied in blockage of specific steps in their replicative lifecycle in human cells. However, an alternative approach is reducing the molecular cleavage of the viral surface spike protein of SARS-CoV-2 to prevent viral entry into epithelial cells.
Relational Expectations and Transactional Obligations: Incompatible Psychological Contracts and Triadic Employment Relationships
Authors: Handy Jocelyn , Gardner Dianne , Davy Doreen
Published: June 2020

This research investigated the triangular employment relationship between organizations, temporary staffing agencies, and clerical temporary workers using the conceptual framework of the psychological contract. The rapid growth in triadic employment relationships is well documented; however, there is limited research into the interlocking psychological contracts between the three parties. This research advances our understanding of the mechanisms underlying triangular psychological contracts by drawing attention to the ways in which people’s beliefs concerning their own obligations toward others may be incommensurate with their expectations of other parties. Findings are based on semistructured interviews with 10 client organization representatives, 10 staffing agency consultants, and 20 female clerical temporaries working in Auckland, New Zealand. The interviews revealed that the three sets of participants held mutually incompatible expectations, which were shaped by their differing positions and power bases within the temporary labor market. Each group expected, or wanted, the other parties to behave toward them as if a relational psychological contract existed but perceived their obligations toward others in more transactional terms. In consequence, the expectations, goals, and actions of the three sets of participants often conflicted, creating a range of adverse outcomes, which were unintended by, and problematic for, each group within the triangular employment relationship.
Regional Anesthetic Blocks for Donor Site Pain in Burn Patients: A Meta-Analysis on Efficacy, Outcomes, and Cost
Authors: Grunzweig Katherine A. , Son Ji , Kumar Anand R.
Published: June 2020

Background:

Skin graft donor site pain significantly affects pain management, narcotic use, and hospital length of stay. This study is intended to evaluate the efficacy of regional anesthesia in the burn population to decrease narcotic consumption and to assess the impact on hospitalization costs.

Methods:

PubMed/MEDLINE, Embase, and ScienceDirect were searched with the following inclusion criteria: comparative studies, adult populations, burn patients, autologous skin grafting, regional nerve blocks, and traditional narcotic regimens. Outcomes assessed included narcotic consumption, pain scores, and opioid side effects. Meta-analysis obtained pooled values for morphine consumption and side effects. Cost analysis was performed using published data in the literature.

Results:

Final analysis included 101 patients. Cumulative morphine consumption at 72 hours was lower for patients treated with regional anesthesia versus patient-controlled analgesia (PCA; single shot 25 ± 12 mg, continuous regional 23 ± 16 mg, control 91.5 ± 24.5 mg; P < .05). Regional anesthesia decreased nausea/vomiting ( P < .05) and lowered subjective pain scores. Regional anesthesia interventions cost less than PCA, single shot less than continuous ( P < .05).

Conclusion:

Regional anesthesia at skin graft donor sites significantly decreases narcotic consumption in burn patients. Regional anesthesia is cost-effective, decreases side effects, and may result in shorter hospital stays due to improved pain management.
Developing Entrepreneurial Competencies in Vietnam: Evidence from the Bac Ninh Province
Authors: Devetag Maria Giovanna , Zazzerini Giovanni , Tuan Nguyen Quang , Hung Doan Quang
Published: June 2020

The article presents the results of a survey conducted among colleges and enterprises located in Bac Ninh, Vietnam, with the aim of identifying skills and competencies required by local enterprises versus those that colleges develop and transfer to their students. The final aim is to spot gaps and discrepancies which may help explain the students’ current low level of employability and, consequently, define lines of intervention that may help reduce the gaps. The key finding emerging from the research is the relatively low importance given by colleges to entrepreneurial competencies compared with what enterprises want.
Contrast-Enhanced Ultrasound: Identification of Neovascularization Permits Characterization of Vulnerable Carotid Plaques
Authors: Baun Jim
Published: June 2020

Objective:

Carotid atherosclerotic vascular disease (ASVD) represents an ongoing health problem and is responsible for a significant proportion of all cerebral ischemic events (CIEs).

Method:

A review of the literature was performed on the application of contrast-enhanced ultrasound (CEUS) to enhance the diagnosis of ASVD and further avoid CIEs.

Results:

Cerebral ischemic events are those resulting from reduction or cessation of perfusion to localized regions of the brain made manifest by neurological, typically stroke-like, symptoms. Traditional triplex ultrasound evaluation is a reliable and widely established method of identifying carotid ASVD lesions and grading the accompanying degree of focal stenoses and their hemodynamic impact. While this information plays an integral role in determining management of patients with significant carotid ASVD, it is less useful in classifying individual lesions as “vulnerable” or not. Vulnerable lesions are those that, based on their histological and morphological features, predispose a patient to an increased risk of a CIE due to plaque or thrombus embolization.

Conclusions:

The addition of CEUS to carotid artery diagnostic studies offers new potential in identifying vulnerable plaques and predicting which patients will progress to sequelae associated with a cerebral ischemic event.
Luboržákite, Mn2AsSbS5, a new member of pavonite homologous series from Vorontsovskoe gold deposit, Northern Urals, Russia
Authors: Kasatkin Anatoly V. , Makovicky Emil , Plášil Jakub , Škoda Radek , Agakhanov Atali A. , Stepanov Sergey Y. , Palamarchuk Roman S.
Published: June 2020

Luboržákite, ideally Mn2AsSbS5, is a new mineral from the Vorontsovskoe gold deposit, Northern Urals, Russia. It forms long-prismatic crystals up to 70 × 20 μm and anhedral grains of the same size embedded in the matrix of Mn-bearing dolomite and Mn-bearing calcite. Associated minerals include pyrite, orpiment, realgar, stibnite, aktashite, alabandite, boscardinite, chabournéite, coloradoite, clerite, écrinsite, gold, routhierite, sphalerite and twinnite. Luboržákite is black, opaque with metallic lustre and has a black streak. It is brittle and has an uneven fracture. No cleavage and parting have been observed. Mohs hardness is 4–4½.Dcalc= 4.181 g cm–3. In reflected light, luboržákite is tin-white, weakly anisotropic with rotation tints varying from dark grey to grey. The chemical composition of luboržákite is (wt.%; electron microprobe, WDS mode): Mn 21.23, Cu 0.29, Ag 0.56, Pb 1.90, As 15.25, Sb 27.03, S 33.23, total 99.49. The empirical formula based on the sum of all atoms = 9 apfu is Mn1.86Pb0.04Ag0.03Cu0.02As0.98Sb1.07S5.00. The new mineral is monoclinic, space groupC2/mwitha= 12.5077(6),b= 3.8034(2),c= 16.0517(8) Å, β = 94.190(4)°,V= 761.57(6) Å3andZ= 4. The crystal structure of luboržákite was solved from the single-crystal X-ray diffraction data toR= 0.0383 for 712 observed reflections withI> 3σ(I). Luboržákite is a new member of the heterochemical isostructural series of ‘unit-cell twinned’ structures, named the pavonite series. The new mineral honours Lubor Žák, a prominent Czech crystallographer and the professor of the Charles University in Prague, Czech Republic.
A comparison among PCNL, Miniperc and Ultraminiperc for lower calyceal stones between 1 and 2 cm: a prospective, comparative, multicenter and randomised study
Authors: Bozzini Giorgio , Aydogan Tahsin Batuhan , Müller Alexander , Sighinolfi Maria Chiara , Besana Umberto , Calori Alberto , Lorenzo Berti , Govorov Alexander , Pushkar Dmitry Y. , Pini Giovannalberto , Pastore Antonio Luigi , Romero-Otero Javier , Rocco Bernardo , Buizza Carlo
Published: June 2020

Background

Conventional Percutaneous Lithotripsy (PCNL) has been an effective, successful and easy approach for especially > 1 cm sized calyceal stones however risks of complications and nephron loss are inevitable. Our aim is to compare the efficacy and safety of PCNL, MiniPerc (MP) and UltraMiniPerc (UMP) for lower calyceal stones between 1 and 2 cm with a multicenter prospective randomized study.

Methods

Between January 2015 and June 2018, 132 consecutive patients with single lower calyceal stone were enrolled. Patients were randomized in three groups; A: PCNL; B: MP; C: UMP. 44 patients for the Group A, 47 for Group B and 41 for Group C. Exclusion criterias were the presence of coagulation impairments, age of < 18 or > 75, presence of infection or serious comorbidities. Patients were controlled with computerized tomography scan after 3 months. A negative CT or an asymptomatic patient with stone fragments < 3 mm size were the criteria to assess the stone-free status. Patient characteristics, stone free rates (SFR) s, complications and re-treatment rates were analyzed.

Results

The mean stone size were 16.38, 16.82 and 15.23 mm respectively in Group A, B and C(p = 0.34). The overall SFR was significantly higher in Group A (86.3%) and B (82.9%) as compared to Group C (78%)(p < 0.05). The re-treatment rate was significantly higher in Group C (12.1%) and complication rates was higher in Group A (13.6%) as compared to others(p < 0.05). The hospitalization was significantly shorter in Group C compared to Group A (p = 0.04).

Conclusions

PCNL and MP showed higher efficacy than UMP to obtain a better SFR. Auxiliary and re-treatment rates were higher in UMP. On the other hand for such this kind of stones PCNL had more complications. Overall evaluation favors MP as a better indication in stones 1–2 cm size.
Estimating the contribution of different age strata to vaccine serotype pneumococcal transmission in the pre vaccine era: a modelling study
Authors: Flasche Stefan , Lipsitch Marc , Ojal John , Pinsent Amy
Published: June 2020

Background

Herd protection through interruption of transmission has contributed greatly to the impact of pneumococcal conjugate vaccines (PCVs) and may enable the use of cost-saving reduced dose schedules. To aid PCV age targeting to achieve herd protection, we estimated which population age groups contribute most to vaccine serotype (VT) pneumococcal transmission.

Methods

We used transmission dynamic models to mirror pre-PCV epidemiology in England and Wales, Finland, Kilifi in Kenya and Nha Trang in Vietnam where data on carriage prevalence in infants, pre-school and school-aged children and adults as well as social contact patterns was available. We used Markov Chain Monte Carlo methods to fit the models and then extracted the per capita and population-based contribution of different age groups to VT transmission.

Results

We estimated that in all settings, < 1-year-old infants cause very frequent secondary vaccine type pneumococcal infections per capita. However, 1–5-year-old children have the much higher contribution to the force of infection at 51% (28, 73), 40% (27, 59), 37% (28, 48) and 67% (41, 86) of the total infection pressure in E&W, Finland, Kilifi and Nha Trang, respectively. Unlike the other settings, school-aged children in Kilifi were the dominant source for VT infections with 42% (29, 54) of all infections caused. Similarly, we estimated that the main source of VT infections in infants are pre-school children and that in Kilifi 39% (28, 51) of VT infant infections stem from school-aged children whereas this was below 15% in the other settings.

Conclusion

Vaccine protection of pre-school children is key for PCV herd immunity. However, in high transmission settings, school-aged children may substantially contribute to transmission and likely have waned much of their PCV protection under currently recommended schedules.
Upregulation of ARHGAP30 attenuates pancreatic cancer progression by inactivating the β-catenin pathway
Authors: Zhou Yongping , Hua Zhiyuan , Zhu Ye , Wang Liying , Chen Fangming , Shan Ting , Zhou Yunhai , Dai Tu
Published: June 2020

Background

Pancreatic cancer is a highly malignant gastrointestinal cancer that can widely metastasize during the early stage of disease, and it is associated with one of the worst prognoses among cancers. In this study, we aimed to investigate the function of Rho GTPase-activating protein 30 (ARHGAP30) in pancreatic cancer cells and thus propose a novel therapy for pancreatic cancer.

Methods

ARHGAP30 expression in tumor tissues from patients with pancreatic cancer as well as cell lines was detected using immunohistochemistry (IHC), real-time polymerase chain reaction, and western blotting. Cell proliferation, transwell, and apoptosis assays were performed and the levels of related proteins were determined after ARHGAP30 knockdown or overexpression. Additionally, in vivo experiments were performed on nude mice.

Results

ARHGAP30 expression was found to be significantly increased in tumor tissues from patients with pancreatic cancer as well as in pancreatic cancer cell lines. IHC and prognostic analyses indicated that patients with high ARHGAP30 expression had a good prognosis. ARHGAP30 overexpression significantly decreased pancreatic cancer cell proliferation and metastasis; promoted apoptosis; reduced β-catenin, B-cell lymphoma 2 (Bcl-2), matrix metalloproteinase-2 (MMP2), and MMP9 expression; and increased Bcl-2-associated X protein (Bax) and cleaved caspase-3 expression. ARHGAP30 knockdown elicited the opposite effects. The effects of ARHGAP30 knockdown were potently attenuated by the β-catenin inhibitor XAV939. ARHGAP30 knockdown-induced RHOA activity was potently attenuated by the RHOA inhibitor CCG1423. In vivo, ARHGAP30 overexpression significantly inhibited lung metastasis in nude mice and increased the survival of mice with lung metastases.

Conclusions

Our findings indicate that ARHGAP30 may function as a tumor suppressor in pancreatic cancer progression by regulating the expression of related genes and the β-catenin pathway.
Transformative medical education: must community-based traineeship experiences be part of the curriculum? A qualitative study
Authors: Massé Julie , Dupéré Sophie , Martin Élisabeth , Lévesque Martine C.
Published: June 2020

Background

There are shortcomings in medical practitioners’ capacity to adapt to the particular needs of people experiencing circumstances of social vulnerability. Clinical traineeships create opportunities for the acquisition of knowledge, competencies, attitudes, and behaviors. However, some authors question the learnings to be made through classical clinical training pathways. This article explores the learnings gained from a traineeship experience within a community-based clinical setting intended for patients experiencing social vulnerability and operating under an alternative paradigm of care. To our knowledge, there is little research intended to identify and understand what medical trainees gain from their experience in such contexts.

Methods

This exploratory qualitative study is based on twelve interviews with practicing physicians who completed a traineeship atLa Maison Bleue(Montreal, Canada) and three interviews conducted with key informants involved in traineeship management. Based on Mezirow’s theory of transformational learning, data were analyzed according to L’Écuyer’s principles of qualitative content analysis. NVivo software was used.

Results

The main learnings gained through the traineeship are related to (1) greater awareness of beliefs, assumptions and biases through prejudice deconstruction, cultural humility and critical reflection on own limitations, power and privileges; (2) the development of critical perspectives regarding the health care system; (3) a renewed vision of medical practice involving a less stigmatizing approach, advocacy, empowerment, interdisciplinarity and intersectorality; and (4) strengthened professional identity and future practice orientation including confirmation of interest for community-based practice, the identification of criteria for choosing a future practice setting, and commitment to becoming an actor of social change. Certain characteristics of the setting, the patients and the learner’s individual profile are shown to be factors that promote these learnings.

Conclusions

This article highlights how a traineeship experience within a clinical setting intended for a clientele experiencing circumstances of social vulnerability and operating under an alternative paradigm presents an opportunity for transformative learning and health practice transformation toward renewed values of health equity and social justice. Our findings suggest medical traineeships in community-based clinical settings are a promising lead to foster the development of fundamental learnings that are conducive to acceptable and equitable care for people experiencing social vulnerability.
SARS-CoV-2 COVID-19 susceptibility and lung inflammatory storm by smoking and vaping
Authors: Kaur Gagandeep , Lungarella Giuseppe , Rahman Irfan
Published: June 2020

The current pandemic of COVID-19 has caused severe morbidity and mortality across the globe. People with a smoking history have severe disease outcomes by COVID-19 infection. Epidemiological studies show that old age and pre-existing disease conditions (hypertension and diabetes) result in severe disease outcome and mortality amongst COVID-19 patients. Evidences suggest that the S1 domain of the SARS-CoV-2 (causative agent of COVID-19) membrane spike has a high affinity towards the angiotensin-converting enzyme 2 (ACE2) receptor found on the host’s lung epithelium. Likewise, TMPRSS2 protease has been shown to be crucial for viral activation thus facilitating the viral engulfment. The viral entry has been shown to cause ‘cytokine storm’ involving excessive production of pro-inflammatory cytokines/chemokines including IL-6, TNF-α, IFN-γ, IL-2, IL-7, IP-10, MCP-3 or GM-CSF, which is augmented by smoking. Future research could target these inflammatory-immunological responses to develop effective therapy for COVID-19. This mini-review provides a consolidated account on the role of inflammation and immune responses, proteases, and epithelial permeability by smoking and vaping during SARS-CoV2 infection with future directions of research, and provides a list of the potential targets for therapies particularly controlling cytokine storms in the lung.
A comprehensive custom panel evaluation for routine hereditary cancer testing: improving the yield of germline mutation detection
Authors: Velázquez Carolina , Lastra Enrique , Avila Cobos Francisco , Abella Luis , de la Cruz Virginia , Hernando Blanca Ascensión , Hernández Lara , Martínez Noemí , Infante Mar , Durán Mercedes
Published: June 2020

Background

In the context of our Regional Program of Hereditary Cancer, individuals fulfilling the criteria are tested for germline mutations to subsequently establish the clinical management. Our standard diagnostic approach focuses on sequencing a few classic high-risk genes, a method that frequently renders uninformative genetic results. This study aims to examine the improved yield offered by an On-Demand panel.

Methods

We designed an On-Demand panel for the analysis of 35-genes associated with inherited cancer susceptibility in a total of 128 cases of Hereditary Breast and Ovarian Cancer (HBOC) and Hereditary Nonpolyposis Colorectal Cancer (HNPCC).

Results

Eighteen deleterious mutations were detected, in both routinely (BRCA2, MLH1, MSH2, PMS2) and non-routinely (ATM, BLM, BRIP1, CHEK2, MUTYH) tested genes. The screening extended to 35 genes rendered by patients carrying several- up to 6-Variants of Unknown Significance (VUS). Moreover, we confirmed the splicing disruption at RNA level for a not previously reported BRIP1 splicing mutation. Using an On-Demand panel, we identified 18 pathogenic mutation carriers, seven of which would have gone unnoticed with traditional analysis.

Conclusions

Our results reinforce the utility of NGS gene panels in the diagnostic routine to increase the performance of genetic testing, especially in individuals from families with overlapping cancer phenotypes.
Extrasynaptic CaMKIIα is involved in the antidepressant effects of ketamine by downregulating GluN2B receptors in an LPS-induced depression model
Authors: Tang Xiao-Hui , Zhang Guang-Fen , Xu Ning , Duan Gui-Fang , Jia Min , Liu Ru , Zhou Zhi-Qiang , Yang Jian-Jun
Published: June 2020

Background

A subanesthetic dose of ketamine provides rapid and effective antidepressant effects, but the molecular mechanism remains elusive. It has been reported that overactivation of extrasynaptic GluN2B receptors is associated with the antidepressant effects of ketamine and the interaction between GluN2B and calcium/calmodulin-dependent protein kinase IIα (CaMKIIα) is important for GluN2B localization and activity. Here, we tested whether changes of CaMKIIα and GluN2B are involved in the antidepressant effects of ketamine.

Methods

Lipopolysaccharide (LPS) was injected intraperitoneally (i.p.) into male C57BL/6 mice. For the interventional study, mice were administrated with ketamine (10 mg/kg, i.p.) or a CaMKIIα inhibitor KN93. Behavioral alterations were evaluated by open-field, novelty-suppressed feeding, and forced-swimming tests. Physiological functions were evaluated by the body weight and fur coat state of mice. The levels of p-CaMKIIα, CaMKIIα, p-GluN2B, GluN2B, p-CREB, CREB, BDNF, GluR1, and GluR2 in the hippocampus were detected by western blotting. The interaction between GluN2B and CaMKIIα was studied using immunoprecipitation assay and small interfering RNA (siRNA) assays. The colocalizations of GluN2B/PSD95 and p-GluN2B/PSD95 were detected by immunofluorescence. The long-term potentiation (LTP) in SC-CA1 of the hippocampus was detected by electrophysiology.

Results

LPS injection induced depression-like behaviors, which were accompanied by significant increases in extrasynaptic p-CaMKIIα expression, extrasynaptic GluN2B localization, and phosphorylation and decreases in p-CREB, BDNF, and GluR1 expressions and LTP impairment. These changes were prevented by ketamine administration. Immunoprecipitation assay revealed that LPS induced an increase in the p-CaMKIIα–GluN2B interaction, which was attenuated by ketamine administration. SiRNA assay revealed that CaMKIIα knockdown reduced the level and number of clusters of GluN2B in the cultured hippocampal neurons. KN93 administration also reduced extrasynaptic p-CaMKIIα expression, extrasynaptic GluN2B localization, and phosphorylation and exerted antidepressant effects.

Conclusion

These results indicate that extrasynaptic CaMKIIα plays a key role in the cellular mechanism of ketamine’s antidepressant effect and it is related to the downregulation of extrasynaptic GluN2B localization and phosphorylation.
Classical and lectin complement pathways and markers of inflammation for investigation of susceptibility to infections among healthy older adults
Authors: LaFon David C. , Thiel Steffen , Kim Young-il , Dransfield Mark T. , Nahm Moon H.
Published: June 2020

Background

There is increasing recognition of the significance of chronic, low-level inflammation in older adults, or “inflammaging.” Innate immune responses and host-bacterial interactions are recognized as key factors in inflammaging. Inflammatory cytokine IL-6, and complement protein C1q have been identified as biomarkers for the development of frailty and aging-related diseases. Older adults are also susceptible to infections with serotypes of Streptococcus pneumoniae that bind ficolin-2, a component of the lectin complement pathway, and low ficolin-2 levels could possibly be involved in such susceptibility.

Methods

The aim of our study was to evaluate complement pathway components and biomarkers for inflammaging among older adults in order to investigate potential innate immune mechanisms that may account for susceptibility to infections in this population. We compared inflammatory markers, as well as components/activity of the classical and lectin complement pathways between healthy older and younger adults. We hypothesized that older adults would have higher levels of inflammatory markers and C1q, and lower levels of lectin pathway components. Older (≥70 years old) and younger (19–54 years old) adults without significant smoking history or chronic medical conditions were eligible for participation. Inflammatory markers (IL-6, TNF-α, CRP), classical complement pathway activity (CH50) and protein levels (C1q, C3, C4), and lectin pathway (MBL levels/activity, CL-L1, MASP-1/2/3, MAp44, MAp19, and H/M/L-ficolin) were compared between groups.

Results

Older adults had significantly higher mean levels of IL-6 and TNF-α. There were no significant differences in lectin pathway components between older and younger adults. Unexpectedly, mean C1q was significantly higher in the younger group in both unadjusted and adjusted analyses. There was also a significant association between race and C1q levels, but this association did not completely account for the observed differences between age groups.

Conclusions

We did not observe deficiencies in lectin pathway components to account for increased susceptibility to ficolin-binding serotypes of S. pneumoniae. Elevated levels of inflammatory cytokines in older adults are suggestive of inflammaging. However, the observed age and race-associated changes in C1q have not been previously reported in the populations included in our study. These findings are relevant to the investigation of C1q in aging-related pathology, and for its proposed role as a biomarker for frailty and disease.
Assessment of two POC technologies for CD4 count in Morocco
Authors: Elharti Elmir , Abbadi Halima , Bensghir Rajae , Marhoum El Filali Kamal , Elmrabet Hajar , Oumzil Hicham
Published: June 2020

Background

In the era of “test and treat strategy”, CD4 testing remains an important tool for monitoring HIV-infected individuals. Since conventional methods of CD4 count measurement are costly and cumbersome, POC CD4 counting technique are more affordable and practical for countries with limited resources. Before introducing such methods in Morocco, we decided to assess their reliability.

Methods

In this study 92 blood samples from HIV-infected patients, were tested by PIMA and FACSPresto to derive CD4 count. Flow cytometry using FacsCalibur, was used as reference method for CD4 count comparison. Linear regression, Bland–Altman analysis were performed to assess correlation and agreement between these POC methods and the reference method. In addition, sensitivity and specificity, positive predictive value (PPV), negative predictive value (NPV) and misclassification percentage at 350 and 200 CD4 count thresholds; were also determined. Finally, because FACSPresto can also measure hemoglobin (Hb) concentration, 52 samples were used to compare FACSPresto against an automated hematology analyzer.

Results

The coefficient of determination R2 was 0.93 for both methods. Bland–Altman analysis displayed a mean bias of − 32.3 and − 8.1 cells/µl for PIMA and FACSPresto, respectively. Moreover, with a threshold of 350 CD4 count, PIMA displayed a sensitivity, specificity, PPV, NPV, were 88.57%, 94.12%, 91.18%, 92.31%; respectively. FACSPresto showed 88.23%, 96.23%, 93.75% and 92.73%; respectively. Furthermore, the upward misclassification percentage was 8.57 and 5.88%, for PIMA and FACSPresto, respectively; whereas the downward misclassification percentage was 7.84% and 7.54%; respectively. With 200 cells/µl threshold, PIMA had a sensitivity, specificity, PPV and NPV of 83.33%, 98.53%, 93.75% and 95.71%, respectively. Regarding FACSPresto, sensitivity, specificity, PPV and NPV was 82.35%, 98.57%, 88.57% and 95.83%; respectively. Upward misclassification percentage was 5.56% and 5.88%, for PIMA and FACSPresto, respectively; whereas downward misclassification percentage was 4.41% and 4.29%; respectively. Finally, the hemoglobin measurement evaluation displayed an R2 of 0.80 and a mean bias of − 0.12 with a LOA between − 1.75 and 1.51.

Conclusion

When compared to the reference method, PIMA and FACSPresto have shown good performance, for CD4 counting. The introduction of such POC technology will speed up the uptake of patients in the continuum of HIV care, in our country.
Core-labelling technique (CLT): a novel combination of the ingrowth-core method and tracer technique for deep root study
Authors: Han Eusun , Dresbøll Dorte Bodin , Thorup-Kristensen Kristian
Published: June 2020

Background

Ingrowth-core method is a useful tool to determine fine root growth of standing crops by inserting root-free soil in mesh-bags for certain period of time. However, the root density observed by the method does not directly explain the nutrient uptake potential of crop plants as it varies over soil depth and incubation time. We have inserted an access-tube up to 4.2 m of soil depth with openings directly under crop plants, through which ingrowth-cores containing labelled soil with nutrient tracers were installed, called core-labelling technique (CLT). The main advantage of CLT would be its capacity to determine both root density and root activity from the same crop plants in deep soil layers. We tested the validity of the new method using a model crop species, alfalfa (Medicago sativa) against three depth-levels (1.0, 2.5 and 4.2 m), three sampling spots with varying distance (0–0.36, 0.36–0.72 and > 5 m from core-labelled spot), two sampling times (week 4 and 8), and two plant parts (young and old leaves) under two field experiments (spring and autumn).

Results

Using CLT, we were able to observe both deep root growth and root activity up to 4.2 m of soil depth. Tracer concentrations revealed that there was no sign of tracer-leakage to adjacent areas which is considered to be advantageous over the generic tracer-injection. Root activity increased with longer incubation period and tracer concentrations were higher in younger leaves only for anionic tracers.

Conclusions

Our results indicate that CLT can lead to a comprehensive deep root study aiming at measuring both deep root growth and root activity from the same plants. Once produced and installed, the access-tubes and ingrowth-cores can be used for a long-term period, which reduces the workload and cost for the research. Therefore, CLT has a wide range of potential applications to the research involving roots in deep soil layers, which requires further confirmation by future experiments.