bluuebunny/crossref_metadata_2025 huggingface dataset:
Performing business risk assessment with real-world data set and data visualization
Authors: Perdana Arif , Tan Janet
Published: May 2021

While real-world data may be publicly available and easily accessible, data require context to be delivered in a classroom. Apart from providing students experience working with real-world data for data analytics, this case also provides an example to university instructors on how to contextualize the real-world data set for teaching. This case equips students with relevant skills in data analytics that are aligned with the industry need. The context that we provided in this teaching case is applicable to undergraduate courses. We applied this case as one of business information system–related courses for the first-year university students.
The Relationship Between Information Technology Capabilities, Organizational Intelligence, and Competitive Advantage
Authors: Awamleh Fawwaz , Ertugan Ahmet
Published: May 2021

This study aimed to identify the mediating role of organizational intelligence between information technology capabilities and competitive advantage. The data were collected from a sample of 224 employees of various managerial positions in e-commerce companies in Jordan. Process macro v3.5 was applied to process data collected. The study concluded that information technology capabilities and organizational intelligence play an essential role in raising and improving competitive advantage and responding to business environmental changes. Empirical evidence indicated a need to develop information technology capabilities via organizational intelligence due to its positive impact on competitive advantage.
Comparing the Socioeconomic Development of G7 and BRICS Countries and Resilience to COVID-19: An Entropy–MARCOS Framework
Authors: Biswas Sanjib , Majumder Shuvendu , Dawn Suman Kumar
Published: May 2021

In this article, we aim to compare the socioeconomic development (SED) of the countries listed in G7 (representing developed nations) and BRICS (Brazil, Russia, India, China and South Africa—developing countries). Further, we intend to delve into the nexus between the SED of a country and its resilience to the current pandemic, COVID-19. The initial apprehension is that a country with better SED can show better resilience. To test this assumption, we consider seven socioeconomic indicators representing income, employment status, educational level, health condition, government expenditures in essential areas, like health, research and development, and gender equality and apply a compromise solution–based multi-criteria decision analysis (MCDA) framework. Next, we consider three parameters, namely infected cases (IC), recovery rate (RR), and death rate (DR), as explanatory proxy variables to indicate the resilience of the countries to COVID-19 spread. Finally, we examine the association between the SED and resilience of the countries. The results show that the SED of a country does not lead to better resilience to COVID-19.
Comparison of the Sterilization Efficiency of 3 Disinfectants for Dropped Anterior Cruciate Ligament Grafts: A Systematic Review and Meta-analysis
Authors: Shen Xianyue , Qin Yanguo , Zuo Jianlin , Liu Tong , Xiao Jianlin
Published: May 2021

Background:

The inadvertent contamination of anterior cruciate ligament (ACL) grafts can occur if they are accidentally dropped on the floor during ACL reconstruction. There has been no meta-analysis conducted to compare the sterilization efficiency of the different disinfectants used on dropped ACL grafts.

Purpose:

To compare the sterilization efficiency of 3 disinfectants to decontaminate ACL grafts as necessary.

Study Design:

Systematic review.

Methods:

A systematic literature review was performed using the MEDLINE, Embase, and Cochrane Library databases. All studies reporting the management of dropped or contaminated grafts were considered for this meta-analysis.

Results:

A total of 7 studies meeting inclusion criteria were identified from a literature search. The pooled results of this meta-analysis indicated that the rate of positive cultures of ACL grafts dropped on the operating room floor was 44.9% and that the commonly contaminated microbes were staphylococci and bacilli. The meta-analysis results indicated that the sterilization efficiency of a 4% chlorhexidine solution was superior to an antibiotic solution (odds ratio [OR], 0.17 [95% CI, 0.05-0.57]; P = .004) and a 10% povidone-iodine solution (OR, 0.04 [95% CI, 0.01-0.20]; P < .0001). Further, the antibiotic solution was superior to the 10% povidone-iodine solution (OR, 0.20 [95% CI, 0.07-0.55]; P = .002).

Conclusion:

The results of our meta-analysis demonstrated that staphylococci and bacilli were the most common contaminants on dropped ACL grafts and that decontamination using a 4% chlorhexidine solution more reliably disinfected ACL grafts. This information can help to guide surgeons as regards appropriate remedial measures.
A Blinded Randomized Trial Comparing 2 Needle Gauges for Fine‐Needle Biopsy of Thyroid Nodules
Authors: Shumrick Christopher M. , Simmonds Jonathan C. , Ogden Lorna L. , Snowden Cindi A. , Dhingra Jagdish K.
Published: May 2021

Objective

To compare diagnostic capability and patient pain between 25‐gauge (25G) and 27G needles for ultrasound‐guided fine‐needle biopsy of thyroid nodules.

Study Design

Prospective blinded randomized trial.

Setting

Thyroid clinic in otolaryngology practice in a community.

Methods

A prospective randomized blinded trial was conducted on 148 thyroid nodules in 107 patients undergoing ultrasound‐guided fine‐needle biopsy. Needle gauge was randomized to individual nodule. Patients were blinded to the needle size used. All specimens were assessed via the Bethesda System for Reporting Thyroid Cytopathology and assigned a morphologic quantitative score based on number of thyroid cells and lymphocytes, amount of colloid, and degree of blood/fibrin artifact in each sample. Patient pain experience was scored. A chi‐square test was used to compare nondiagnostic rates, and differences in cytologic morphology and pain scores were compared with 2‐sample Student t tests.

Results

Of the 148 nodules, 77 were biopsied with 25G needles and 71 with 27G needles. Twenty‐five percent (19/77) of the samples obtained with 25G needles yielded a nondiagnostic cytology result (Bethesda category 1) as compared with 11% (8/70) in the 27G group (P =. 0282; 95% CI, 1.47%‐25.97%). On average, samples from 25G needles had a higher blood/fibrin quantitative score (P =. 043; 95% CI, −0.64 to −0.010). There were no differences in pain between groups.

Conclusion

Use of a 27G needle for fine‐needle biopsies is not only safe and feasible but desirable and highly recommended, as it yields better diagnostic information.
Development of pre-molded internal thread on composite tubes
Authors: Takano Atsushi , Kitamura Ryuta , Masai Takuma , Nishino Sayaka
Published: May 2021

Premolded internal threads on composite tubes were developed. The composite tubes with threads on both ends were made using a mandrel with a male thread. The threads can be applied to struts with adjustable end fits and composite pressure vessels with threaded caps that enable disassembly for inspection and repair. Carbon fiber-reinforced plastic (CFRP) prepregs were laid up on a mandrel, wrapped with shrink tape, and cured in an oven. The threads were built-in, without using machine cutting, and the fibers on the thread were continuous through the thread and tubes for high strength. The thread was alternately rounded, convex, and concave in shape to enable CFRP prepregs to be laid up. Two types of specimen were made and tested. The layup sequence of specimen A was [0/h/90/h/0/h(1/2)]s, and that of specimen B was [0/h/90/h/90/h/0/h/90/h/90/h/90/h/90/h/0/h/90/90/0], where “h” denotes a helical layer along the concave part of the threads. The relation between load and strain is nonlinear because of the rounded shape of the threads; however, a simple and closed form analytical model was able to predict the strength of the threads and design of the threads. The model was compared with the experimental results. In addition, an application of threads for the pressure vessel of the hybrid rocket motor is also reported. The combustion test proceeded without failure. Visual inspection after the test indicated that the threads and tubes were not damaged, and thus, they can be applied to high-pressure and high-temperature rocket motors.
Overexpression of wild-type IL-7Rα promotes T-cell acute lymphoblastic leukemia/lymphoma
Authors: Silva Ana , Almeida Afonso R. M. , Cachucho Ana , Neto João L. , Demeyer Sofie , de Matos Mafalda , Hogan Thea , Li Yunlei , Meijerink Jules , Cools Jan , Grosso Ana Rita , Seddon Benedict , Barata João T.
Published: May 2021

Tight regulation of IL-7Rα expression is essential for normal T-cell development. IL-7Rα gain-of-function mutations are known drivers of T-cell acute lymphoblastic leukemia (T-ALL). Although a subset of patients with T-ALL display high IL7R messenger RNA levels and cases with IL7R gains have been reported, the impact of IL-7Rα overexpression, rather than mutational activation, during leukemogenesis remains unclear. In this study, overexpressed IL-7Rα in tetracycline-inducible Il7r transgenic and Rosa26 IL7R knockin mice drove potential thymocyte self-renewal, and thymus hyperplasia related to increased proliferation of T-cell precursors, which subsequently infiltrated lymph nodes, spleen, and bone marrow, ultimately leading to fatal leukemia. The tumors mimicked key features of human T-ALL, including heterogeneity in immunophenotype and genetic subtype between cases, frequent hyperactivation of the PI3K/Akt pathway paralleled by downregulation of p27Kip1 and upregulation of Bcl-2, and gene expression signatures evidencing activation of JAK/STAT, PI3K/Akt/mTOR and Notch signaling. Notably, we also found that established tumors may no longer require high levels of IL-7R expression upon secondary transplantation and progressed in the absence of IL-7, but remain sensitive to inhibitors of IL-7R–mediated signaling ruxolitinib (Jak1), AZD1208 (Pim), dactolisib (PI3K/mTOR), palbociclib (Cdk4/6), and venetoclax (Bcl-2). The relevance of these findings for human disease are highlighted by the fact that samples from patients with T-ALL with high wild-type IL7R expression display a transcriptional signature resembling that of IL-7–stimulated pro-T cells and, critically, of IL7R-mutant cases of T-ALL. Overall, our study demonstrates that high expression of IL-7Rα can promote T-cell tumorigenesis, even in the absence of IL-7Rα mutational activation.
Natural attenuation along subsurface flow paths based on modeling and monitoring of a pesticide metabolite from three case studies
Authors: Herrmann Marco , Sur Robin
Published: May 2021

Background

Groundwater—especially for the use as drinking water—is a strictly protected resource in the existing guidelines for pesticide registration and drinking water protection in the EU. One aspect that has hardly played a role in this context so far is the attenuation of pesticide concentrations along the flow path from the regulatory leaching concentration at a depth of 1 m below the applied field to raw water abstraction systems. The soil metabolite N,N-dimethylsulfamide (DMS) is formed from two fungicidal substances: tolylfluanid and dichlofluanid. According to the EU guidance document on relevant metabolites in groundwater, DMS is a “non-relevant” metabolite. However, long-term application of the two active substances on permanent crops has resulted in elevated and quantifiable amounts of DMS in groundwater catchment areas of water supplying plants. Therefore, in the case of DMS, substantial monitoring data is available. This enables in combination with groundwater modeling, a quantitative analysis of the natural attenuation of DMS concentrations over time and distance. To this end, extensive real-world data from three case studies of drinking water catchment areas in Germany were analyzed.

Results

The environmental fate of DMS in soil and groundwater was evaluated according to the respective data determined at the study sites. Analyses using monitoring data and combined modeling approaches as well, were performed to obtain comparable results. These merged outcomes from monitoring and modeling show total attenuation factors of 12–93 from leachate at 1 m depth down to monitoring wells—close to raw water collection. If concentration attenuation further downwards to collected raw water is considered, the overall attenuation factor is even higher (40–246).

Conclusions

The conditions at the catchment areas of the three case studies are very diverse, thus providing a wide range of attenuating conditions. When following the path of DMS from its formation in soil below a treated field, to its leaching into the aquifer, and within the aquifer down to the raw water collection site, its concentration in water is continuously and consistently decreasing. The results from DMS represent conservative estimations due to non-sorptive, quick transport processes. Extended to other sorptive solutes, it represents the lower end of expected attenuation. Therefore, natural pesticide concentration attenuation processes are suggested for the consideration in regulatory pesticide risk assessments for a more realistic yet still protective evaluation of expected concentrations in raw water.
Structural variations in papaya genomes
Authors: Liao Zhenyang , Zhang Xunxiao , Zhang Shengcheng , Lin Zhicong , Zhang Xingtan , Ming Ray
Published: May 2021

Background

Structural variations (SVs) are a type of mutations that have not been widely detected in plant genomes and studies in animals have shown their role in the process of domestication. An in-depth study of SVs will help us to further understand the impact of SVs on the phenotype and environmental adaptability during papaya domestication and provide genomic resources for the development of molecular markers.

Results

We detected a total of 8083 SVs, including 5260 deletions, 552 tandem duplications and 2271 insertions with deletion being the predominant, indicating the universality of deletion in the evolution of papaya genome. The distribution of these SVs is non-random in each chromosome. A total of 1794 genes overlaps with SV, of which 1350 genes are expressed in at least one tissue. The weighted correlation network analysis (WGCNA) of these expressed genes reveals co-expression relationship between SVs-genes and different tissues, and functional enrichment analysis shows their role in biological growth and environmental responses. We also identified some domesticated SVs genes related to environmental adaptability, sexual reproduction, and important agronomic traits during the domestication of papaya. Analysis of artificially selected copy number variant genes (CNV-genes) also revealed genes associated with plant growth and environmental stress.

Conclusions

SVs played an indispensable role in the process of papaya domestication, especially in the reproduction traits of hermaphrodite plants. The detection of genome-wide SVs and CNV-genes between cultivated gynodioecious populations and wild dioecious populations provides a reference for further understanding of the evolution process from male to hermaphrodite in papaya.
Spanish-dementia knowledge assessment scale (DKAS-S): psychometric properties and validation
Authors: Carnes A. , Barallat-Gimeno E. , Galvan A. , Lara B. , Lladó A. , Contador-Muñana J. , Vega-Rodriguez A. , Escobar M. A. , Piñol-Ripoll G.
Published: May 2021

Background

Alzheimer’s disease (AD) is the most frequent cause of cognitive impairment. Community knowledge of the disease has proven to be a very important aspect of the development of interventions and the evaluation of their effectiveness. However, it is necessary to have standardized and recognized tools in different languages. The aim of the current study was to develop a cross-cultural adaptation of the Spanish Dementia Knowledge Assessment Scale (DKAS-S) and to assess their psychometric properties with cohorts of health students and professional and non-professional caregivers of AD patients from several regions of Spain.

Methods

We developed and translated the DKAS into Spanish following the forward-back-forward translation procedure. Then, we performed a cross-sectional study to assess the validity, reliability and feasibility of the DKAS-S. We also performed an analysis to obtain test-retest reliability measures. The study was performed in four medical centres across three regions in Spain. From May to September 2019, we administered the scale to students, professional and non-professional caregivers; including a subgroup of non-professional caregivers of patients with early-onset AD (< 65 years).

Results

Eight hundred forty-six volunteer participants completed the DKAS-S: 233 students (mean age 26.3 ± 9.2 years), 270 professional caregivers (mean age 42.5 ± 11.7 years) and 343 non-professional caregivers of AD patients. (mean age was 56.4 ± 13.16). The DKAS-S showed good internal consistency (Cronbach’s α = 0.819) and good test-retest reliability (time 1: 28.1 ± 8.09 vs time 2: 28.8 ± 7.96; t = − 1.379; p = 0.173). Sensitivity to change was also significant in a subgroup of 31 students who received education related to AD and dementias between each administration (time 1: 25.6 ± 6.03) to (time 2: 32.5 ± 7.12; t = − 5.252, p = 0.000). The validity of the construct was verified by confirmatory factor analysis, although there were challenges in the inclusion of some items in the original 4 factors.

Conclusions

The 25-item DKAS-S showed good psychometric properties for validity and reliability and the factorial analysis when it was administered to a population of students and professional and non-professional caregivers. It was a useful instrument for measuring levels of knowledge about dementia in Spanish population.
Use of the Arabin pessary in women at high risk for preterm birth: long-term experience at a single tertiary center in Malaysia
Authors: Rahman Rahana Abd , Atan Ixora Kamisan , Ali Anizah , Kalok Aida Mohd , Ismail Nor Azlin Mohamed , Mahdy Zaleha Abdullah , Ahmad Shuhaila
Published: May 2021

Background

Spontaneous preterm birth is a global issue that contributed to perinatal morbidities and mortalities worldwide. The study aimed to describe the experience at UKM Medical Center in managing women at high risk for spontaneous preterm birth using the Arabin pessary.

Methods

This is a retrospective observational study involving 58 pregnancies from 1st January 2013 to 31st December 2019. Inclusion criteria were previous mid-trimester miscarriage and/or preterm birth, previous cervical surgery or short cervical length on routine sonogram. The demographic data, characteristics of each pregnancy and details of outcomes and management were described.

Results

The majority of women were Malay with mean age and body mass index of 32.9 ± 4.2 years and 27.1 ± 6.3 kg/m2respectively. The most frequent indications for Arabin pessary insertion were previous mid-trimester miscarriage (46.4%) and early preterm birth (17.2%). A total of 73.4% of these women had the pessary inserted electively at a mean cervical length of 31.6 ± 9.1 mm at median gestation of 15.0 weeks. They were managed as outpatient (56.9%), inpatient (24.1%) or mixed (19.0%) with combination of progestogen (81.0%) and 53.4% received antenatal corticosteroids. Spontaneous preterm birth at or more than 34 weeks gestation occurred in 74.1% with birthweight at or more than 2000 g (82.4%). Despite cervical funneling in 12 women (20.7%), 66.7% delivered at or later than 34 weeks gestation and 2 (16.7%) resulted in miscarriage.

Conclusions

Insertion of the Arabin pessary is beneficial to prevent spontaneous preterm birth in pregnant women who are at high risk. In particular, early insertion and close monitoring allows the best possible outcomes.

Trial registration

This study was retrospectively registered with ClinicalTrials.gov (NCT04638023) on 20/11/2020.
Orthotopic model of lung cancer: isolation of bone micro-metastases after tumor escape from Osimertinib treatment
Authors: Jarry Ulrich , Bostoën Mégane , Pineau Raphaël , Chaillot Laura , Mennessier Valentine , Montagne Pierre , Motte Emilie , Gournay Marjorie , Le Goff Arnaud , Guillaudeux Thierry , Pedeux Rémy
Published: May 2021

Background

Osimertinib is a third generation tyrosine kinase inhibitor (TKI) that targets the epidermal growth factor receptor (EGFR) in lung cancer. However, although this molecule is not subject to some of the resistance mechanisms observed in response to first generation TKIs, ultimately, patients relapse because of unknown resistance mechanisms. New relevant non-small cell lung cancer (NSCLC) mice models are therefore required to allow the analysis of these resistance mechanisms and to evaluate the efficacy of new therapeutic strategies.

Methods

Briefly, PC-9 cells, previously modified for luciferase expression, were injected into the tail vein of mice. Tumor implantation and longitudinal growth, almost exclusively localized in the lung, were evaluated by bioluminescence. Once established, the tumor was treated with osimertinib until tumor escape and development of bone metastases.

Results

Micro-metastases were detected by bioluminescence and collected for further analysis.

Conclusion

We describe an orthotopic model of NSCLC protocol that led to lung primary tumor nesting and, after osimertinib treatment, by metastases dissemination, and that allow the isolation of these small osimertinib-resistant micro-metastases. This model provides new biological tools to study tumor progression from the establishment of a lung tumor to the generation of drug-resistant micro-metastases, mimicking the natural course of the disease in human NSCLC patients.
Invasive breast Cancer treatment in Tanzania: landscape assessment to prepare for implementation of standardized treatment guidelines
Authors: Sood Rupali , Masalu Nestory , Connolly Roisin M. , Chao Christina A. , Faustine Lucas , Mbulwa Cosmas , Anderson Benjamin O. , Rositch Anne F.
Published: May 2021

Background

Incidence of breast cancer continues to rise in low- and middle-income countries, with data from the East African country of Tanzania predicting an 82% increase in breast cancer from 2017 to 2030. We aimed to characterize treatment pathways, receipt of therapies, and identify high-value interventions to increase concordance with international guidelines and avert unnecessary breast cancer deaths.

Methods

Primary data were extracted from medical charts of patients presenting to Bugando Medical Center, Tanzania, with breast concerns and suspected to have breast cancer. Clinicopathologic features were summarized with descriptive statistics. A Poisson model was utilized to estimate prevalence ratios for variables predicted to affect receipt of life-saving adjuvant therapies and completion of therapies. International and Tanzanian guidelines were compared to current care patterns in the domains of lymph node evaluation, metastases evaluation, histopathological diagnosis, and receptor testing to yield concordance scores and suggest future areas of focus.

Results

We identified 164 patients treated for suspected breast cancer from April 2015–January 2019. Women were predominantly post-menopausal (43%) and without documented insurance (70%). Those with a confirmed histopathology diagnosis (69%) were 3 times more likely to receive adjuvant therapy (PrR [95% CI]: 3.0 [1.7–5.4]) and those documented to have insurance were 1.8 times more likely to complete adjuvant therapy (1.8 [1.0–3.2]). Out of 164 patients, 4% (n = 7) received concordant care based on the four evaluated management domains. The first most common reason for non-concordance was lack of hormone receptor testing as 91% (n = 144) of cases did not undergo this testing. The next reason was lack of lymph node evaluation (44% without axillary staging) followed by absence of abdominopelvic imaging in those with symptoms (35%) and lack of histopathological confirmation (31%).

Conclusions

Patient-specific clinical data from Tanzania show limitations of current breast cancer management including axillary staging, receipt of formal diagnosis, lack of predictive biomarker testing, and low rates of adjuvant therapy completion. These findings highlight the need to adapt and adopt interventions to increase concordance with guidelines including improving capacity for pathology, developing complete staging pathways, and ensuring completion of prescribed adjuvant therapies.
Health coaching provided by registered nurses described: a systematic review and narrative synthesis
Authors: Barr Jennieffer A. , Tsai Lily P.
Published: May 2021

Aims

The aim of this systematic review and narrative synthesis was to identify how and why health coaching is delivered by Registered Nurses.

Design

Systematic review and narrative synthesis.

Data sources

Articles were identified through a search of CINAHL, Medline, Scopus, and PsychINFO databases. Articles published in English between 2010 and 2021 were included.

Review Methods

Quality appraisal of relevant literature was independently undertaken by two authors to assess for risk of bias. The Critical Appraisal Skills Program (CASP) was used to appraise quality of potential papers.

Results

A main purpose of coaching by Registered Nurses is to optimise patient self-care. How coaching was conducted varied across studies, with the most common coaching approaches via telephone or online. Majority of studies highlight some effectiveness of coaching by nurses; however, some results were inconclusive. Health coaching generally reduced mental distress. Other benefits reported by patients included reduced pain and fatigue. Outcomes for changing lifestyle behaviours were mixed. However, for health coaching to be efficient greater evidence is needed to determine length of time to use coaching, number of habits to focus on to produce change, and to determine best training for coaches.

Conclusions

Registered Nurses are most suitable for implementing health coaching for self-care, including preventing and managing chronic illness and recovering from situations like post-surgical needs. Nurses already promote health, and therefore, are skilled in educating people in self-care. Coaching is an additional strategy for motivating, targeting and assessing progress of self-care. Extending the scope of nursing practice to routinely coach in self-care would be ideal.
An agent-based model clarifies the importance of functional and developmental integration in shaping brain evolution
Authors: Avin Shahar , Currie Adrian , Montgomery Stephen H.
Published: May 2021

Background

Vertebrate brain structure is characterised not only by relative consistency in scaling between components, but also by many examples of divergence from these general trends.. Alternative hypotheses explain these patterns by emphasising either ‘external’ processes, such as coordinated or divergent selection, or ‘internal’ processes, like developmental coupling among brain regions. Although these hypotheses are not mutually exclusive, there is little agreement over their relative importance across time or how that importance may vary across evolutionary contexts.

Results

We introduce an agent-based model to simulate brain evolution in a ‘bare-bones’ system and examine dependencies between variables shaping brain evolution. We show that ‘concerted’ patterns of brain evolution do not, in themselves, provide evidence for developmental coupling, despite these terms often being treated as synonymous in the literature. Instead, concerted evolution can reflect either functional or developmental integration. Our model further allows us to clarify conditions under which such developmental coupling, or uncoupling, is potentially adaptive, revealing support for the maintenance of both mechanisms in neural evolution. Critically, we illustrate how the probability of deviation from concerted evolution depends on the cost/benefit ratio of neural tissue, which increases when overall brain size is itself under constraint.

Conclusions

We conclude that both developmentally coupled and uncoupled brain architectures can provide adaptive mechanisms, depending on the distribution of selection across brain structures, life history and costs of neural tissue. However, when constraints also act on overall brain size, heterogeneity in selection across brain structures will favour region specific, or mosaic, evolution. Regardless, the respective advantages of developmentally coupled and uncoupled brain architectures mean that both may persist in fluctuating environments. This implies that developmental coupling is unlikely to be a persistent constraint, but could evolve as an adaptive outcome to selection to maintain functional integration.
Benefit of switching to mepolizumab from omalizumab in severe eosinophilic asthma based on patient characteristics
Authors: Liu Mark C. , Chipps Bradley , Munoz Xavier , Devouassoux Gilles , Bergna Miguel , Smith Steven G. , Price Robert G. , Galkin Dmitry V. , Azmi Jay , Mouneimne Dalal , Albers Frank C. , Chapman Kenneth R.
Published: May 2021

Background

The OSMO study assessed the efficacy of switching to mepolizumab in patients with severe eosinophilic asthma that was uncontrolled whilst receiving omalizumab. The objective of this analysis was to assess the proportion of patients achieving pre-defined improvements in up to four efficacy outcomes and the relationship between patient baseline characteristics and treatment response.

Methods

This was a post hoc analysis of OSMO study data (GSK ID:204471; ClinicalTrials.gov No. NCT02654145). Patients with severe eosinophilic asthma uncontrolled by high-dose inhaled corticosteroids, other controller(s) and omalizumab subcutaneously (≥ 4 months) were switched to mepolizumab 100 mg administered subcutaneously. Endpoints included the proportion of responders—i.e. patients achieving a pre-defined clinical improvement in ≥ 1 of the following outcomes: (1) Asthma Control Questionnaire (ACQ)-5 score (≥ 0.5-points), (2) St George’s Respiratory Questionnaire (SGRQ) total score (≥ 4-points), (3) pre-bronchodilator forced expiratory volume in 1s (FEV1; ≥ 100 mL), all at Week 32, and (4) annualised rate of clinically significant exacerbations (≥ 50% reduction).

Results

Of the 145 patients included, 94%, 83%, 63% and 31% were responders for ≥ 1, ≥ 2, ≥ 3 and 4 outcomes, respectively; 75% and 78% were ACQ-5 and SGRQ score responders, and 50% and 69% were FEV1 and exacerbation responders. Subgroup analyses demonstrated improvements irrespective of baseline blood eosinophil count, prior omalizumab treatment regimen/duration, comorbidities, prior exacerbation history, maintenance oral corticosteroid use, ACQ-5 and SGRQ scores, and body weight/body mass index.

Conclusions

After switching to mepolizumab, almost all patients with uncontrolled severe eosinophilic asthma on omalizumab achieved a beneficial response in ≥ 1 clinical outcome. Improvements were observed regardless of baseline characteristics.

Trial registration This manuscript is a post hoc analysis of data from the OSMO study. ClinicalTrials.gov, NCT02654145. Registered January 13, 2016.
Transposition of cardiovascular outcome trial effects to the real-world population of patients with type 2 diabetes
Authors: Sciannameo V. , Berchialla P. , Avogaro A. , Fadini G. P. ,   DARWIN-T2D Network, Consoli Agostino , Formoso Gloria , Grossi Giovanni , Pucci Achiropita , Sesti Giorgio , Andreozzi Francesco , Capobianco Giuseppe , Gatti Adriano , Bonadonna Riccardo , Zavaroni Ivana , DeiCas Alessandra , Felace Giuseppe , Li Volsi Patrizia , Buzzetti Raffaella , Leto Gaetano , Sorice Gian Pio , D’Angelo Paola , Morano Susanna , Bossi Antonio Carlo , Duratorre Edoardo , Franzetti Ivano , Morpurgo Paola Silvia , Orsi Emanuela , Querci Fabrizio , Boemi Massimo , D’Angelo Federica , Petrelli Massimiliano , Aimaretti Gianluca , Karamouzis Ioannis , Cavalot Franco , Saglietti Giuseppe , Cazzetta Giuliana , Cervone Silvestre , Devangelio Eleonora , Lamacchia Olga , Arena Salvatore , Di Benedetto Antonino , Frittitta Lucia , Giordano Carla , Piro Salvatore , Rizzo Manfredi , Chianetta Roberta , Mannina Carlo , Anichini Roberto , Penno Giuseppe , Solini Anna , Fattor Bruno , Bonora Enzo , Cigolini Massimo , Lapolla Annunziata , Chilelli Nino Cristiano , Simioni Natalino , Frison Vera , Vinci Carmela
Published: May 2021

Background

Transferring results obtained in cardiovascular outcome trials (CVOTs) to the real-world setting is challenging. We herein transposed CVOT results to the population of patients with type 2 diabetes (T2D) seen in routine clinical practice and who may receive the medications tested in CVOTs.

Methods

We implemented the post-stratification approach based on aggregate data of CVOTs and individual data of a target population of diabetic outpatients. We used stratum-specific estimates available from CVOTs to calculate expected effect size for the target population by weighting the average of the stratum-specific treatment effects according to proportions of a given characteristic in the target population. Data are presented as hazard ratio (HR) and 95% confidence intervals.

Results

Compared to the target population (n = 139,708), the CVOT population (n = 95,816) was younger and had a two to threefold greater prevalence of cardiovascular disease. EMPA-REG was the CVOT with the largest variety of details on stratum-specific effects, followed by TECOS, whereas DECLARE and PIONEER-6 had more limited stratum-specific information. The post-stratification HR estimate for 3 point major adverse cardiovascular event (MACE) based on EMPA-REG was 0.88 (0.74–1.03) in the target population, compared to 0.86 (0.74–0.99) in the trial. The HR estimate based on LEADER was 0.88 (0.77–0.99) in the target population compared to 0.87 (0.78–0.97) in the trial. Consistent results were obtained for SUSTAIN-6, EXSCEL, PIONEER-6 and DECLARE. The effect of DPP-4 inhibitors observed in CVOTs remained neutral in the target population.

Conclusions

Based on CVOT stratum-specific effects, cardiovascular protective actions of glucose lowering medications tested in CVOTs are transferrable to a much different real-world population of patients with T2D.
Evidence‐based priorities of under‐served pregnant and parenting adolescents: addressing inequities through a participatory approach to contextualizing evidence syntheses
Authors: Dion Anna , Klevor Aime , Nakajima Amy , Andersson Neil
Published: May 2021

Purpose

This study describes an interdiscursive evidence-based priority setting process with pregnant and parenting adolescents and their services providers.

Methods

A mixed methods literature review identified studies reporting on perinatal outcomes and experiences of adolescents during pregnancy to 12 months post-partum published in Canada after 2000. We also calculated relative risks for common perinatal risk factors and outcomes for adolescents compared to adult populations from 2012 to 2017 based on data from a provincial database of maternal and newborn outcomes. Two trained peer researchers identified outcomes most relevant to their peers. We shared syntheses results with four service providers and 13 adolescent mothers accessing services at a community service organization, who identified and prioritized their areas of concern. We repeated the process for the identified priority issue and expanded upon it through semi-structured interviews.

Results

Adolescent mothers face higher rates of poverty, abuse, anxiety and depression than do adult mothers. Adolescents prioritized theexperience of judgmentin perinatal health and social services, particularly as it contributed to them being identified as a child protection risk. Secondary priorities included loss of social support and inaccessibility of community resources. The experience of judgment in adolescent perinatal health literature was summarized around: being invisible, seen as incapable and seen as a risk. Adolescent mothers adapted these categories, emphasizing organizational and social barriers.

Conclusions

Young marginalized women are disproportionately affected by inequities in perinatal outcomes, yet their perspectives are rarely centered in efforts to address these inequities. This research addresses health inequities by presenting a robust, transparent and participatory approach to priority setting as a way to better represent the perspectives of those who carry the greatest burden of health inequities in evidence syntheses. In our work, marginalized adolescent parents adapted published literature around the experience and consequences of social stigma on perinatal outcomes, shifting our understanding of root causes and possible solutions.
Effect of nutritional and physical exercise intervention on hospital readmission for patients aged 65 or older: a systematic review and meta-analysis of randomized controlled trials
Authors: Lærum-Onsager Ellisiv , Molin Marianne , Olsen Cecilie Fromholt , Bye Asta , Debesay Jonas , Hestevik Christine Hillestad , Bjerk Maria , Pripp Are Hugo
Published: May 2021

Background

Unplanned readmission may result in consequences for both the individual and society. The transition of patients from hospital to postdischarge settings often represents a discontinuity of care and is considered crucial in the prevention of avoidable readmissions. In older patients, physical decline and malnutrition are considered risk factors for readmission. The purpose of the study was to determine the effects of nutritional and physical exercise interventions alone or in combination after hospital admission on the risk of hospital readmission among older people.

Methods

A systematic review and meta-analysis of randomized controlled studies was conducted. The search involved seven databases (Medline, AMED, the Cochrane Library, CINAHL, Embase (Ovid), Food Science Source and Web of Science) and was conducted in November 2018. An update of this search was performed in March 2020. Studies involving older adults (65 years and above) investigating the effect of nutritional and/or physical exercise interventions on hospital readmission were included.

Results

A total of 11 randomized controlled studies (five nutritional, five physical exercise and one combined intervention) were included and assessed for quality using the updated Cochrane Risk of Bias Tool. Nutritional interventions resulted in a significant reduction in readmissions (RR 0.84; 95% CI 0.70–1.00, p = 0.049), while physical exercise interventions did not reduce readmissions (RR 1.05; 95% CI 0.84–1.31, p-value = 0.662).

Conclusions

This meta-analysis suggests that nutrition support aiming to optimize energy intake according to patients’ needs may reduce the risk of being readmitted to the hospital for people aged 65 years or older.
mTOR regulates GPVI-mediated platelet activation
Authors: Wang Longsheng , Liu Gang , Wu Nannan , Dai Baiyun , Han Shuang , Liu Qiaoyun , Huang Fang , Chen Zhihua , Xu Weihong , Xia Dajing , Gao Cunji
Published: May 2021

Background

Due to mTOR (mammalian/mechanistic target of rapamycin) gene-loss mice die during embryonic development, the role of mTOR in platelets has not been evaluated using gene knockout technology.

Methods

A mouse model with megakaryocyte/platelet-specific deletion of mTOR was established, and be used to evaluate the role of mTOR in platelet activation and thrombus formation.

Results

mTOR−/− platelets were deficient in thrombus formation when grown on low-concentration collagen-coated surfaces; however, no deficiency in thrombus formation was observed when mTOR−/− platelets were perfused on higher concentration collagen-coated surfaces. In FeCl3-induced mouse mesenteric arteriole thrombosis models, wild-type (WT) and mTOR−/− mice displayed significantly different responses to low-extent injury with respect to the ratio of occluded mice, especially within the first 40 min. Additionally, mTOR−/− platelets displayed reduced aggregation and dense granule secretion (ATP release) in response to low doses of the glycoprotein VI (GPVI) agonist collagen related peptide (CRP) and the protease-activated receptor-4 (PAR4) agonist GYPGKF-NH2; these deficiencies were overcame by stimulation with higher concentration agonists, suggesting dose dependence of the response. At low doses of GPVI or PAR agonist, the activation of αIIbβ3 in mTOR−/− platelets was reduced. Moreover, stimulation of mTOR−/− platelets with low-dose CRP attenuated the phosphorylation of S6K1, S6 and Akt Ser473, and increased the phosphorylation of PKCδ Thr505 and PKCε Ser729. Using isoform-specific inhibitors of PKCs (δ, ɛ, and α/β), we established that PKCδ/ɛ, and especially PKCδ but not PKCα/β or PKCθ, may be involved in low-dose GPVI-mediated/mTOR-dependent signaling.

Conclusion

These observations indicate that mTOR plays an important role in GPVI-dependent platelet activation and thrombus formation.
The “black box” of treatment: Patients’ perspective on what works in opioid maintenance treatment for opioid dependence
Authors: Silva Teresa C. , Andersson Fredrik B.
Published: May 2021

Background

A lack of conceptual modeling of how the components of opioid maintenance treatment (OMT) for opioid dependence (OD) work causes it to occasionally be labeled the “black-box” of treatment. This study had a two-fold objective: First, to analyze which factors related to OMT for OD contribute to the abstinence of problematic use of non-prescribed opioids and sustain recovery, from the patients’ perspective; second, to understand which changes OMT produced in the individuals’ lives might significantly contribute to relapse prevention.

Methods

We used qualitative methods of design, inquiry, and analysis from a convenience sample of 19 individuals in a Swedish treatment setting.

Results

All the participants reported previous cycles of problematic use of non-prescribed opioids and other non-prescribed psychoactive substances, treatment, abstinence, recovery, and relapse before starting the current OMT program. During the pre-treatment stage, specific events, internal processes, and social environments enhanced motivation toward abstinence and seeking treatment. During the treatment stage, participants perceived the quality of the human relationships established with primary social groups as important as medication and the individual plan of care in sustaining recovery. From the participants’ perspective, OMT was a turning point in their life course, allowing them a sense of self-fulfillment and the reconstruction of personal and social identity. However, they still struggled with the stigmatization produced by a society that values abstinence-oriented over medication-assisted treatments.

Conclusion

OMT is not an isolated event in individuals’ lives but rather a process occurring within a specific social context. Structural factors and the sense of acceptance and belonging are essential in supporting the transformation. Treatment achievements and the risk for relapse vary over time, so the objectives of the treatment plan must account for characteristics of the pre-treatment stage and the availability and capacity of individuals to restructure their social network, besides the opioid maintenance treatment and institutional social care.
A comparison of three different surgery approaches and methods for neurologically intact thoracolumbar fractures: a retrospective study
Authors: Zhu Chao , Wang Bin , Yin Jian , Liu Xin Hui
Published: May 2021

Objectives

The purpose of this study was to evaluate and compare the feasibility, safety, and efficacy of conventional open pedicle screw fixation (COPSF), percutaneous pedicle screw fixation (PPSF), and paraspinal posterior open approach pedicle screw fixation (POPSF) for treating neurologically intact thoracolumbar fractures.

Methods

We retrospectively reviewed 108 patients who were posteriorly stabilized without graft fusion. Among them, 36 patients underwent COPSF, 38 patients underwent PPSF, and 34 patients underwent POPSF. The clinical outcomes, relative operation indexes, and radiological findings were assessed and compared among the 3 groups.

Results

All of the patients were followed up for a mean time of 20 months. The PPSF group and POPSF group had shorter operation times, lower amounts of intraoperative blood loss, and shorter postoperative hospital stays than the COPSF group (P< 0.05). The radiation times and hospitalization costs were highest in the PPSF group (P< 0.05). Every group exhibited significant improvements in the Cobb angle (CA) and the vertebral body angle (VBA) correction (allP< 0.05). The COPSF group and the POPSF group had better improvements than the PPSF group at 3 days postoperation and the POPSF group had the best improvements in the last follow-up (P< 0.05).

Conclusion

Both PPSF and POPSF achieved similar effects as COPSF while also resulting in lower incidences of injury. PPSF is more advantageous in the early rehabilitation time period, compared with COPSF, but POPSF is a better option when considering the long-term effects, the costs of treatment, and the radiation times.
Activation of spinal dorsal horn astrocytes by noxious stimuli involves descending noradrenergic signaling
Authors: Kawanabe Riku , Yoshihara Kohei , Hatada Izuho , Tsuda Makoto
Published: May 2021

Astrocytes are critical regulators of neuronal function in the central nervous system (CNS). We have previously shown that astrocytes in the spinal dorsal horn (SDH) have increased intracellular Ca2+ levels following intraplantar injection of the noxious irritant, formalin. However, the underlying mechanisms remain unknown. We investigated these mechanisms by focusing on the role of descending noradrenergic (NAergic) signaling because our recent study revealed the essential role of the astrocytic Ca2+ responses evoked by intraplantar capsaicin. Using in vivo SDH imaging, we found that the Ca2+ level increase in SDH astrocytes induced by intraplantar formalin injection was suppressed by ablation of SDH-projecting locus coeruleus (LC)-NAergic neurons. Furthermore, the formalin-induced Ca2+ response was dramatically decreased by the loss of α1A-adrenaline receptors (ARs) in astrocytes located in the superficial laminae of the SDH. Moreover, similar inhibition was observed in mice pretreated intrathecally with an α1A-AR-specific antagonist. Therefore, activation of α1A-ARs via descending LC-NAergic signals may be a common mechanism underlying astrocytic Ca2+ responses in the SDH evoked by noxious stimuli, including chemical irritants.
Activation of the clock gene TIMELESS by H3k27 acetylation promotes colorectal cancer tumorigenesis by binding to Myosin-9
Authors: Cao Meng , Wang Yi , Xiao Yijing , Zheng Dandan , Zhi Chunchun , Xia Xin , Yuan Xiaoqin
Published: May 2021

Background

Colorectal cancer (CRC) is a common tumor characterized by its high mortality. However, the underlying molecular mechanisms that drive CRC tumorigenesis are unclear. Clock genes have important roles in tumor development. In the present study, the expression and functions of clock gene TIMELESS (encoding the Timeless protein) in CRC were investigated.

Methods

Immunohistochemistry, cell proliferation, migration, invasion, EMT and xenograft tumor experiments were used to prove the function of Timeless in the tumorigenesis of CRC. Immunoprecipitation, mass spectrometry, Immunofluorescence and Chromatin immunoprecipitation (ChIP) were utilized to clarify the mechanism of Timeless in regulating CRC tumorigenesis.

Results

We found that Timeless was upregulated in CRC tissues compared with corresponding normal tissues and its expression was closely associated with the TNM stages and overall survival of CRC patients. Functional studies demonstrated that Timeless promoted the proliferation, invasion, and EMT of CRC cells in vitro and in vivo. Mechanistic investigations showed that Timeless activated the β-catenin signal pathway by binding to Myosin-9, which binds to β-catenin to induce its nuclear translocation. The upregulation of Timeless was attributed to CREB-binding protein (CBP)/p300-mediated H3K27 acetylation of the promoter region of Timeless.

Conclusion

Timeless regulates the tumorigenesis of CRC by binding to and regulating myosin-9, suggesting Timeless might be a potential prognostic biomarker and therapeutic target for CRC.