bluuebunny/crossref_metadata_2025 huggingface dataset:
Sex determines the presentation and outcomes in MPN and is related to sex-specific differences in the mutational burden
Authors: Karantanos Theodoros , Chaturvedi Shruti , Braunstein Evan M. , Spivak Jerry , Resar Linda , Karanika Styliani , Williams Donna M. , Rogers Ophelia , Gocke Christopher D. , Moliterno Alison R.
Published: June 2020

The factors underlying the variable presentation and clinical course of myeloproliferative neoplasms (MPNs) remain unclear. The aim of this study was to evaluate the independent effect of sex on MPN presentation and outcomes. A total of 815 patients with essential thrombocytosis, polycythemia vera, or primary myelofibrosis were evaluated between 2005 and 2019, and the association of sex with presenting phenotype, JAK2 V617F burden, progression, and survival was examined. Men presented more often with primary myelofibrosis vs essential thrombocytosis (relative risk, 3.2; P < .001) and polycythemia vera (relative risk, 2.1; P < .001), had higher rates of transformation to secondary myelofibrosis (hazard ratio [HR], 1.55; P = .013) and acute myeloid leukemia (HR, 3.67; P < .001), and worse survival (HR, 1.63; P = .001) independent of age, phenotype at diagnosis, and MPN-specific mutation. Men had higher JAK2 V617F allele burdens in their CD34+ cells (P = .001), acquired more somatic mutations (P = .012) apart from the MPN-specific mutations, and had an increased frequency of 1 (odds ratio, 2.35; P = .017) and 2 (odds ratio, 20.20; P = .011) high-risk mutations independent of age, phenotype, and driver mutation. Male sex is an independent predictor of poor outcomes in MPNs. This seems to be due to an increased risk of non–MPN-specific somatic mutations, particularly high-risk mutations, rather than MPN-specific mutation allele frequency. Conversely, disease progression in female subjects is more dependent on JAK2 mutation allele burden than on acquisition of other somatic mutations. Sex should be considered in prognostic models and when evaluating therapeutic strategies in MPNs.
Shorter telomere length following lung transplantation is associated with clinically significant leukopenia and decreased chronic lung allograft dysfunction-free survival
Authors: Courtwright Andrew M. , Lamattina Anthony M. , Takahashi Mai , Trindade Anil J. , Hunninghake Gary M. , Rosas Ivan O. , Agarwal Suneet , Raby Benjamin A. , Goldberg Hilary J. , El-Chemaly Souheil
Published: June 2020

Patients with short telomeres and interstitial lung disease may have decreased chronic lung allograft dysfunction (CLAD)-free survival following lung transplantation. The relationship between post-transplant telomere length and outcomes following lung transplantation has not been characterised among all recipients, regardless of native lung disease.

This was a single-centre prospective cohort study. Consenting transplant recipients had their telomere length measured using quantitative real-time PCR assays on peripheral blood collected at the time of surveillance bronchoscopy. We assessed the association between early post-transplant telomere length (as measured in the first 100 days) and CLAD-free survival, time to clinically significant leukopenia, cytomegalovirus (CMV) viraemia, chronic kidney disease, and acute cellular rejection. We also assessed the association between rate of telomere shortening and CLAD-free survival.

Telomere lengths were available for 98 out of 215 (45.6%) recipients who underwent lung transplant during the study period (median measurement per patient=2 (interquartile range, 1–3)). Shorter telomere length was associated with decreased CLAD-free survival (hazard ratio (HR)=1.24; 95% CI=1.03–1.48; p=0.02), leukopenia requiring granulocyte colony-stimulating factor (HR=1.17, 95% CI=1.01–1.35, p=0.03), and CMV viraemia among CMV-mismatch recipients (HR=4.04, 95% CI=1.05–15.5, p=0.04). Telomere length was not associated with acute cellular rejection or chronic kidney disease. Recipients with more rapid loss in telomere length (defined as the highest tertile of telomere shortening) did not have worse subsequent CLAD-free survival than those without rapid loss (HR=1.38, 95% CI=0.27–7.01, p=0.70).

Shorter early post-transplant telomere length is associated with decreased CLAD-free survival and clinically significant leukopenia in lung transplant recipients, regardless of native lung disease.
Messinian or Pleistocene valley incision within the Southern Alps
Authors: Winterberg Sascha , Picotti Vincenzo , Willett Sean D.
Published: June 2020

Many of the valleys on the southern slope of the Alps are over-deepened, having bedrock valley floors well below sea level. This has typically been attributed to incision that occurred during the Messinian Salinity Crisis (MSC) when sea level dropped by hundreds of meters, leading to incision of many of the margins of the Mediterranean. We reassess this interpretation by documenting the correct elevation of the valley floor of the Adige river, one of the major valleys draining the Southern Alps, and by estimating the vertical motion of that valley floor since the end of Messinian incision. We re-evaluated the bedrock incision in the Adige valley using existing borehole data and seismic profiles. We estimate the vertical post-Messinian uplift using thermochronometric data that reveal the removed rock mass and then infer the expected isostatic uplift. These data are combined to reconstruct paleo-river gradients and to test viability of incision profiles. We find that the erosive surfaces in the drill holes restore to a paleo-elevation well below estimates of the Messinian Salinity Crisis (MSC) sea level. Restored valley gradients are often reversed compared to todays river gradients, as the uplift correction is higher upstream. A Messinian age of the erosional unconformities within the Alps can therefore be excluded based on the current best estimates of Messinian Mediterranean sea level and post-Messinian rock uplift. Pleistocene glacial erosion left a major signature on the geomorphology of the valleys, which is documented by glacially over-deepended valleys in the northern Alps. These valleys are not influenced by the Messinian sea-level drawdown. Therefore, it is suggested that the over-deepened valleys on the southern slope of the Alps are also glacial in origin.
Simulation Study of the Double-Gate Tunnel Field-Effect Transistor with Step Channel Thickness
Authors: Zhang Maolin , Guo Yufeng , Zhang Jun , Yao Jiafei , Chen Jing
Published: June 2020

Double-gate tunnel field-effect transistor (DG TFET) is expected to extend the limitations of leakage current and subthreshold slope. However, it also suffers from the ambipolar behavior with the symmetrical source/drain architecture. To overcome the ambipolar current, asymmetry must be introduced between the source and drain. In this paper, we investigate the performances of DG TFET with step channel thickness (SC TFET) by utilizing the 2D simulation. The asymmetry between source and drain is introduced through the step channel thickness; hence, the ambipolar behavior is expected to be relieved. The results show that the SC TFET exhibits significant reduction of ambipolar current compared with the conventional DG TFET. The mechanisms of SC TFET are thoroughly discussed to explore the physical insight. The impacts introduced by the structure parameters on onset voltage, subthreshold slope, drain current in on-state and ambipolar-state are also exhibited in determining the optimal structure.
Public knowledge and attitudes towards bystander cardiopulmonary resuscitation (CPR) in Ghana, West Africa
Authors: Anto-Ocrah Martina , Maxwell Nick , Cushman Jeremy , Acheampong Emmanuel , Kodam Ruth-Sally , Homan Christopher , Li Timmy
Published: June 2020

Background and objectives

Early bystander cardiopulmonary resuscitation (CPR) is one of the most important predictors of out-of-hospital cardiac arrests (OHCA) survival. There is a dearth of literature on CPR engagement in countries such as Ghana, where cardiovascular events are increasingly prevalent. In this study, we sought to evaluate Ghanaians’ knowledge of and attitudes towards bystander CPR, in the context of the country’s nascent emergency medicine network.

Methods

Capitalizing on the growing ubiquity and use of social media across the country, we used a novel social media sampling strategy for this study. We created, pre-tested, and distributed an online survey, using the two most utilized social media platforms in Ghana: WhatsApp and Facebook. An airtime data incentive of 5 US dollars, worth between 5 and 10 GB of cellular data based on mobile phone carrier, was provided as incentive. Inclusion criteria were (1) ≥ 18 years of age, (2) living in Ghana. Survey participants were encouraged to distribute the survey within their own networks to expand its reach. We stratified participants’ responses by healthcare affiliation, and further grouped healthcare workers into ambulance and non-ambulance personnel. We used chi-square (χ2)/Fisher’s Exact tests to compare differences in responses between the groups. Based on the question “have you ever heard of CPR?”, an alpha of 0.05 and a 95% confidence interval, we expected to have 80% power to detect a 15% difference in responses between lay and healthcare providers with an estimated sample size of 246 study participants.

Results

The survey was launched on 8 July 2019 and closed approximately 51 h post-launch. With a 64% completion rate and 479 unique survey completions, the study was overpowered at 96% power, to detect differences in responses between the groups. There was geographic representation across all 10 historic regions of Ghana. Over half (57.8%, n = 277) of the respondents were non-medically affiliated, and 71.9% were women. Healthcare workers were more aware of CPR than lay respondents (96.5% vs 68.1%; p < 0.001). Eighty-five percent of respondents were aware that CPR involves chest compressions, and almost 70% indicated that “mouth to mouth” is a necessary component of CPR. Fewer than 10% were unwilling to administer CPR. Lack of skills (44.9%) and fear of causing harm (25.5%) were barriers noted by respondents for not administering CPR. Notably, a quarter of ambulance workers reported never having received CPR training. If they were to witness a collapse, 62.0% would call an ambulance, and 32.6% would hail a taxi.

Conclusion

The majority of participants are willing to perform CPR. Contextualized training that emphasizes hands-only CPR and builds participants’ confidence may increase bystander willingness and engagement.
Performance of a three-level triage scale in live triage encounters in an emergency department in Hong Kong
Authors: Lam Rex Pui Kin , Kwok Shing Lam , Chaang Vi Ka , Chen Lujie , Lau Eric Ho Yin , Chan Kin Ling
Published: June 2020

Background

Despite its continued use in many low-volume emergency departments (EDs), 3-level triage systems have not been extensively studied, especially on live triage cases. We have modified from the Australasian Triage Scale and developed a 3-level triage scale, and sought to evaluate its validity, reliability, and over- and under-triage rates in real patient encounters in our setting.

Method

This was a cross-sectional study in a single ED with 24,000 attendances per year. At triage, each patient was simultaneously assessed by a triage nurse, an adjudicator (the “criterion standard”), and a study nurse independently. Predictive validity was determined by comparing clinical outcomes, such as hospitalization, across triage levels. The discriminating performance of the triage tool in identifying patients requiring earlier medical attention was determined. Inter-observer reliability between the triage nurse and criterion standard, and across providers were determined using kappa statistics.

Results

In total, 453 triage ratings of 151 triage cases, involving 17 ED triage nurses and 57 nurse pairs, were analysed. The proportion of hospital admission significantly increased with a higher triage rating. The performance of the scale in identifying patients requiring earlier medical attention was as follows: sensitivity, 68.2% (95% CI 45.1–86.1%); specificity, 99.2% (95% CI 95.8–100%); positive predictive value, 93.8% (95% CI 67.6–99.1%); and negative predictive value, 94.8% (95% CI 90.8–97.1%). The over-triage and under-triage rates were 0.7% and 4.6%, respectively. Agreement between the triage nurse and criterion standard was substantial (quadratic-weighted kappa = 0.76, 95% CI, 0.60–0.92,p< 0.001), so was the agreement across nurses (quadratic-weighted kappa = 0.81, 95% CI 0.65–0.97,p< 0.001).

Conclusions

The 3-level triage system appears to have good validity and reasonable reliability in a low-volume ED setting. Further studies comparing 3-level and prevailing 5-level triage scales in live triage encounters and different ED settings are warranted.
Effects of nicotine on regional blood flow in the olfactory bulb in response to olfactory nerve stimulation
Authors: Uchida Sae , Kagitani Fusako
Published: June 2020

This study examined the effect of olfactory nerve stimulation on regional cerebral blood flow and assessed the effect of intravenous nicotine administration on this response in anesthetized rats. Regional cerebral blood flow was measured with laser Doppler flowmetry or laser speckle contrast imaging. Unilateral olfactory nerve stimulation for 5 s produced current (≥ 100 μA) and frequency-dependent (≥ 5 Hz) increases in blood flow in the olfactory bulb ipsilateral to the stimulus. The increased olfactory bulb blood flow peaked at 30 ± 7% using stimulus parameters of 300 μA and 20 Hz. Nerve stimulation did not change frontal cortical blood flow or mean arterial pressure. The intravenous injection of nicotine (30 μg/kg) augmented the olfactory bulb blood flow response to nerve stimulation (20 Hz, 300 μA) by approximately 1.5-fold (60-s area after the stimulation). These results indicate that olfactory nerve stimulation increases olfactory bulb blood flow, and the response is potentiated by the activation of nicotinic cholinergic transmission.
Multilocus sequence analysis for the taxonomic updating and identification of the genus Proteus and reclassification of Proteus genospecies 5 O’Hara et al. 2000, Proteus cibarius Hyun et al. 2016 as later heterotypic synonyms of Proteus terrae Behrendt et al. 2015
Authors: Dai Hang , Lu Binghuai , Li Zhenpeng , Huang Zhenzhou , Cai Hongyan , Yu Keyi , Wang Duochun
Published: June 2020

Background

Members of the genus Proteus are mostly opportunistic pathogens that cause a variety of infections in humans. The molecular evolutionary characteristics and genetic relationships among Proteus species have not been elucidated to date. In this study, we developed a multilocus sequence analysis (MLSA) approach based on five housekeeping genes (HKGs) to delineate phylogenetic relationships of species within the genus Proteus.

Results

Of all 223 Proteus strains collected in the current study, the phylogenetic tree of five concatenated HKGs (dnaJ, mdh, pyrC, recA and rpoD) divided 223 strains into eleven clusters, which were representative of 11 species of Proteus. Meanwhile, the phylogenetic trees of the five individual HKGs also corresponded to that of the concatenated tree, except for recA, which clustered four strains at an independent cluster. The evaluation of inter- and intraspecies distances of HKG concatenation indicated that all interspecies distances were significantly different from intraspecies distances, which revealed that these HKG concatenations can be used as gene markers to distinguish different Proteus species. Further web-based DNA-DNA hybridization estimated by genome of type strains confirmed the validity of the MLSA, and each of eleven clusters was congruent with the most abundant Proteus species. In addition, we used the established MLSA method to identify the randomly collected Proteus and found that P. mirabilis is the most abundant species. However, the second most abundant species is P. terrae but not P. vulgaris. Combined with the genetic, genomic and phenotypic characteristics, these findings indicate that three species, P. terrae, P. cibarius and Proteus genospecies 5, should be regarded as heterotypic synonyms, and the species should be renamed P. terrae, while Proteus genospecies 5 has not been named to date.

Conclusions

This study suggested that MLSA is a powerful method for the discrimination and classification of Proteus at the species level. The MLSA scheme provides a rapid and inexpensive means of identifying Proteus strains. The identification of Proteus species determined by the MLSA approach plays an important role in the clinical diagnosis and treatment of Proteus infection.
Transcriptome and metabolite analysis reveal the drought tolerance of foxtail millet significantly correlated with phenylpropanoids-related pathways during germination process under PEG stress
Authors: Yu Aili , Zhao Jinfeng , Wang Zhenhua , Cheng Kai , Zhang Peng , Tian Gang , Liu Xin , Guo Erhu , Du Yanwei , Wang Yuwen
Published: June 2020

Background

Foxtail millet [Setaria italica (L.) P. Beauv.] is an excellent crop known for its superior level of drought tolerance across the world. Especially, less water is needed during its germination period than the other cereal crops. However, the knowledge of the mechanisms underlying the abiotic stress effects on seed germination of foxtail millet is largely unknown.

Results

The water uptake pattern of foxtail millet seeds was ploted during germination period, according to which the germination time course of millet was separated into three phases. We sequenced the transcriptome of foxtail millet seeds, which were treated by PEG during different germination phases after sowing. The transcriptional studies revealed that more DEGs were identified during the further increase in water uptake period (phase III) than during the rapid initial uptake period (phase I) and the plateau period (phase II) under PEG stress. The pathway analysis of DEGs showed that the highly enriched categories were related to phenylpropanoid biosynthesis, plant hormone signal transduction and phenylalanine metabolism during phase III. The 20 phenylpropanoids-related genes of germinating foxtail millet were found to be down-regulated during the further increase in water uptake period under PEG stress. Further expression analysis identified 4 genes of phenylalanine ammonia-lyase, 4-coumarate-CoA ligase 3, cinnamoyl-CoA reductase 1, cationic peroxidase SPC4 in phenylpropanoids-related pathway, which played important roles in foxtail millet in response to PEG stress during different germination periods. The studies of metabolites in phenylpropanoid biosynthesis pathway revealed that higher amount of cinnamic acid was accumulated in germinating seeds under PEG stress, while the contents of p-coumaric acid, caffeic acid, ferulic acid and sinapic acid were decreased. And the effects of five phenolic compounds on germination and growth of foxtail millet showed that 1 mM concentration of cinnamic acid inhibited shoot and root growth, especially root development. Ferulic acid, caffeic acid, sinapic acid and p-coumaric acid could increase the root length and root/sprout in lower concentration.

Conclusions

These findings suggest that key genes and metabolites of foxtail millet related with phenylpropanoids pathway may play prominent roles in the regulation of resistance to drought during germination. Foxtail millet can probably avoid drought by regulating the levels of endogenous allelochemicals.
Mining the stable quantitative trait loci for agronomic traits in wheat (Triticum aestivum L.) based on an introgression line population
Authors: Chen Weiguo , Sun Daizhen , Li Runzhi , Wang Shuguang , Shi Yugang , Zhang Wenjun , Jing Ruilian
Published: June 2020

Background

Human demand for wheat will continue to increase together with the continuous global population growth. Agronomic traits in wheat are susceptible to environmental conditions. Therefore, in breeding practice, priority is given to QTLs of agronomic traits that can be stably detected across multiple environments and over many years.

Results

In this study, QTL analysis was conducted for eight agronomic traits using an introgression line population across eight environments (drought stressed and well-watered) for 5 years. In total, 44 additive QTLs for the above agronomic traits were detected on 15 chromosomes. Among these, qPH-6A, qHD-1A, qSL-2A, qHD-2D and qSL-6A were detected across seven, six, five, five and four environments, respectively. The means in the phenotypic variation explained by these five QTLs were 12.26, 9.51, 7.77, 7.23, and 8.49%, respectively.

Conclusions

We identified five stable QTLs, which includes qPH-6A, qHD-1A, qSL-2A, qHD-2D and qSL-6A. They play a critical role in wheat agronomic traits. One of the dwarf genes Rht14, Rht16, Rht18 and Rht25 on chromosome 6A might be the candidate gene for qPH-6A. The qHD-1A and qHD-2D were novel stable QTLs for heading date and they differed from known vernalization genes, photoperiod genes and earliness per se genes.
Prognosis evaluation of universal acute coronary syndrome: the interplay between SYNTAX score and ApoB/ApoA1
Authors: Wang Xiaotong , Wang Zhongyu , Li Bing , Yang Ping
Published: June 2020

Background

Acute coronary syndrome (ACS) is a group of clinical syndromes associated with substantial morbidity and mortality rate. SYNTAX and SYNTAX II score used to be a reference for surgical selection of coronary revascularization and prognosis evaluation in patients with 3-vessel or left main artery disease. In addition, apoB/apoA1 is an important predictor of ACS risk. This study aims to assess the prognosis value of different kinds of SYNTAX score together with apoB/apoA1 in universal ACS patients (Regardless of ACS type, lesion location and vessel numbers).

Method

Three hundred ninety-six patients with ACS undergoing percutaneous coronary intervention(PCI)and coronary stenting from 2013 to 2014 were chosen and recorded the major adverse cardiovascular and cerebrovascular events (MACCE) and quality of life during the next 5 years. According to SYNTAX and SYNTAX II score, the patients were divided into low-risk, medium-risk and high-risk groups, and the clinical features, MACCE incidence and EQ-5D score at each time points were compared. And the predictive factors of MACCE incidence were analyzed.

Results

① Compared with SYNTAX low-risk group, MACCE incidence in 1 year significantly increased in medium/high risk group (p = 0.011). Compared with SYNTAX II low-risk group, MACCE incidence in 5 years significantly increased in medium and high-risk group (p = 0.032). ② Compared with SYNTAX II low-risk group, cardiovascular mortality in 3 and 5 years significantly elevated in high-risk group (p = 0.001, p<0.001 respectively). ③ Compared with SYNTAX II low and medium-risk group, EQ-5D score in 5 years significantly decreased in high-risk group (p = 0.019, p = 0.023 respectively). ④ ApoB/ApoA1 was more likely to be classified as high risk in SYNTAX/SYNTAX II medium and high-risk group (p = 0.023, p = 0.044 respectively). ⑤ Logistic regression analysis showed that apoB/apoA1 was an independent predictor of MACCE events in hospital and 5 years (p = 0.038, p = 0.016 respectively), SYNTAX score was an independent predictor of MACCE events in 1 year (medium-risk group: p = 0.02; high-risk group: p = 0.015) SYNTAX II score was an independent predictor of MACCE events in 5 yeasrs (p = 0.003).

Conclusions

① SYNTAX score has a high predictive value for short-term prognosis while SYNTAX II score is more predictive of long-term prognosis. ② SYNTAX II score is superior to SYNTAX score in predicting cardiovascular death. ③ The combination of apoB/apoA1 high-risk and SYNTAX II medium and high-risk group is the focus of clinical treatment and long-term follow-up observation.
Laplace approximation, penalized quasi-likelihood, and adaptive Gauss–Hermite quadrature for generalized linear mixed models: towards meta-analysis of binary outcome with sparse data
Authors: Ju Ke , Lin Lifeng , Chu Haitao , Cheng Liang-Liang , Xu Chang
Published: June 2020

Background

In meta-analyses of a binary outcome, double zero events in some studies cause a critical methodology problem. The generalized linear mixed model (GLMM) has been proposed as a valid statistical tool for pooling such data. Three parameter estimation methods, including the Laplace approximation (LA), penalized quasi-likelihood (PQL) and adaptive Gauss–Hermite quadrature (AGHQ) were frequently used in the GLMM. However, the performance of GLMM via these estimation methods is unclear in meta-analysis with zero events.

Methods

A simulation study was conducted to compare the performance. We fitted five random-effects GLMMs and estimated the results through the LA, PQL and AGHQ methods, respectively. Each scenario conducted 20,000 simulation iterations. The data from Cochrane Database of Systematic Reviews were collected to form the simulation settings. The estimation methods were compared in terms of the convergence rate, bias, mean square error, and coverage probability.

Results

Our results suggested that when the total events were insufficient in either of the arms, the GLMMs did not show good point estimation to pool studies of rare events. The AGHQ method did not show better properties than the LA estimation in terms of convergence rate, bias, coverage, and possibility to produce very large odds ratios. In addition, although the PQL had some advantages, it was not the preferred option due to its low convergence rate in some situations, and the suboptimal point and variance estimation compared to the LA.

Conclusion

The GLMM is an alternative for meta-analysis of rare events and is especially useful in the presence of zero-events studies, while at least 10 total events in both arms is recommended when employing GLMM for meta-analysis. The penalized quasi-likelihood and adaptive Gauss–Hermite quadrature are not superior to the Laplace approximation for rare events and thus they are not recommended.
Including ‘seldom heard’ views in research: opportunities, challenges and recommendations from focus groups with British South Asian people with type 2 diabetes
Authors: Prinjha Suman , Miah Nasima , Ali Ebrahim , Farmer Andrew
Published: June 2020

Background

The inclusion of ‘seldom heard’ groups in health and social care research is increasingly seen as important on scientific, policy and ethical grounds. British South Asians, the largest minority ethnic group in the United Kingdom (UK), are under-represented in health research yet over-represented in the incidence of certain conditions such as type 2 diabetes. With the growing requirement of patient involvement in research and the inclusion of diverse populations, methodological guidance on how to include, engage and conduct research with UK South Asian populations is essential if services and interventions are to be relevant and impactful. However, such guidance for researchers is limited.

Methods

The aim of the paper is to reflect on our experiences of conducting focus groups with UK South Asian communities with type 2 diabetes, which involved experienced community partners and researchers working closely together. We discuss the factors that aided the successful delivery of the project, the challenges that we encountered, how we dealt with these, and recommendations.

Results

Our study suggests ways to involve and conduct focus groups with UK South Asian populations. Key considerations are categorised under four headings: co-working with community partners; linguistic competency; cultural competency and awareness; and reflexivity, power and acknowledgement. Having an experienced team of researchers and community experts – with the relevant linguistic and cultural competencies and different kinds of knowledge and skills – was key to the successful delivery of the study. Working collaboratively enabled us to recruit a diverse sample, to navigate the challenges of recruitment, to be present at every discussion which helped contribute to data richness, and to reflect on our own roles in the research process.

Conclusions

Focus groups with UK South Asian communities can be a useful way of exploring new topics and involving seldom heard views. While a useful method, focus groups are only one way of exploring a research topic and provide an insight into context-specific attitudes and views. Future research should explore British South Asian participants’ views on how they would like to be involved in research, including new methods of collecting data and coproducing research.
Symptom management strategies used by older community-dwelling people with multimorbidity and a high symptom burden - a qualitative study
Authors: Eckerblad Jeanette , Waldréus Nana , Stark Åsa Johansson , Jacobsson Lisa Ring
Published: June 2020

Background

Older community-dwelling people with multimorbidity are often not only vulnerable, but also suffer from several conditions that could produce a multiplicity of symptoms. This results in a high symptom burden and a reduced health-related quality of life. Even though these individuals often have frequent contact with healthcare providers they are expected to manage both appropriate disease control and symptoms by themselves or with the support of caregivers. The aim of this study was therefore to describe the symptom management strategies used by older community-dwelling people with multimorbidity and a high symptom burden.

Method

A qualitative descriptive design using face-to-face interviews with 20 community-dwelling older people with multimorbidity, a high healthcare consumption and a high symptom burden. People ≥75 years, who had been hospitalized ≥3 times during the previous year, ≥ 3 diagnoses in their medical records and lived at home were included. The participants were between 79 and 89 years old. Data were analysed using content analyses.

Result

Two main strategy categories were found: active symptom management and passive symptom management. The active strategies include the subcategories; to plan, to distract, to get assistance and to use facilitating techniques. An active strategy meant that participants took matters in their own hands, they could often describe the source of the symptoms and they felt that they had the power to do something to ease their symptoms. A passive symptom management strategy includes the subcategories to give in and to endure. These subcategories often reflected an inability to describe the source of the symptoms as well as the experience of having no alternative other than passively waiting it out.

Conclusions

These findings show that older people with multimorbidity and a high symptom burden employ various symptom management strategies on daily basis. They had adopted appropriate strategies based on their own experience and knowledge. Healthcare professionals might facilitate daily life for older people with multimorbidity by providing guidance on active management strategies with focus on patient’s own experience and preferences.
Influx of diverse, drug resistant and transmissible Plasmodium falciparum into a malaria-free setting in Qatar
Authors: Al-Rumhi Abir , Al-Hashami Zainab , Al-Hamidhi Salama , Gadalla Amal , Naeem Raeece , Ranford-Cartwright Lisa , Pain Arnab , Sultan Ali A. , Babiker Hamza A.
Published: June 2020

Background

Successful control programs have impeded local malaria transmission in almost all Gulf Cooperation Council (GCC) countries: Qatar, Bahrain, Kuwait, Oman, the United Arab Emirates (UAE) and Saudi Arabia. Nevertheless, a prodigious influx of imported malaria via migrant workers sustains the threat of local transmission. Here we examine the origin of imported malaria in Qatar, assess genetic diversity and the prevalence of drug resistance genes in imported Plasmodium falciparum, and finally, address the potential for the reintroduction of local transmission.

Methods

This study examined imported malaria cases reported in Qatar, between 2013 and 2016. We focused on P. falciparum infections and estimated both total parasite and gametocyte density, using qPCR and qRT-PCR, respectively. We also examined ten neutral microsatellites and four genes associated with drug resistance, Pfmrp1, Pfcrt, Pfmdr1, and Pfkelch13, to assess the genetic diversity of imported P. falciparum strains, and the potential for propagating drug resistance genotypes respectively.

Results

The majority of imported malaria cases were P. vivax, while P. falciparum and mixed species infections (P. falciparum / P. vivax) were less frequent. The primary origin of P. vivax infection was the Indian subcontinent, while P. falciparum was mostly presented by African expatriates. Imported P. falciparum strains were highly diverse, carrying multiple genotypes, and infections also presented with early- and late-stage gametocytes. We observed a high prevalence of mutations implicated in drug resistance among these strains, including novel SNPs in Pfkelch13.

Conclusions

The influx of genetically diverse P. falciparum, with multiple drug resistance markers and a high capacity for gametocyte production, represents a threat for the reestablishment of drug-resistant malaria into GCC countries. This scenario highlights the impact of mass international migration on the reintroduction of malaria to areas with absent or limited local transmission.
The correlations between Th1 and Th2 cytokines in human alveolar echinococcosis
Authors: Ma Xiao , Zhang Xuefei , Liu Jia , Liu Yufang , Zhao Cunzhe , Cai Huixia , Lei Wen , Ma Junying , Fan Haining , Zhou Jianye , Liu Na , Zhang Jingxiao , Wang Yongshun , Wang Wei , Zhan Peizhen , Zhang Xiongying , Zhang Qing , Shi Kemei , Liu Peiyun
Published: June 2020

Background

Alveolar echinococcosis (AE) is a zoonotic parasitic disease caused by Echinococcus multilocularis larval tapeworm infections in humans that severely impairs the health of affected patients in the northern hemisphere.

Methods

The expression levels of 20 cytokines associated with AE infection were measured by enzyme-linked immunosorbent assay, and the correlations between these cytokines were analysed in the R programming language.

Results

Serum cytokine levels differed among individuals in both the AE patient and healthy control groups. The results of the correlations among the cytokines showed obvious differences between the two groups. In the AE patients group, Th1 and Th2 cytokines formed a more complicated network than that in the healthy control group.

Conclusions

The altered correlations between Th1 and Th2 cytokines may be closely associated with AE infection, which may provide a new explanation for the essential differences between AE patients and healthy individuals.
Clinical and computed tomography features of extended-spectrum β-lactamase-producing Klebsiella pneumoniae liver abscess
Authors: Ren Yue , Wang Hairui , Chang Zhihui , Liu Zhaoyu
Published: June 2020

Background

Klebsiella pneumoniae (KP) is the primary pathogen associated with pyogenic liver abscesses (PLAs). Moreover, there has been an increase in the proportion of extended-spectrum beta-lactamase (ESBL)-producing KP. However, the clinical and computed tomography (CT) features of liver abscesses caused by ESBL-producing KP have not been separately described. We aimed to compare the clinical and CT features present in patients with ESBL-producing and non-ESBL-producing KP as well as to determine the risk factors for ESBL-producing KP liver abscesses (KPLAs).

Methods

We performed a retrospective analysis of data obtained from the medical records of patients with a first episode of KPLA admitted to Shengjing Hospital of China Medical University between May 2015 and May 2019. We compared the clinical and CT features between patients with ESBL-producing and non-ESBL-producing KPLA.

Results

We enrolled 100 patients with KPLA (14 and 86 in the ESBL-producing and non-ESBL-producing groups, respectively). There was no significant between-group difference in the proportion of patients with comorbid diabetes (71.43% vs. 66.2%, p = 0.086). The ESBL-producing KPLA group had a greater proportion of patients with a history of biliary disease (78.57% vs. 26.74%, p < 0.001) and gastrointestinal malignancy (50% vs. 6.98%, p < 0.001). Multivariate regression analysis showed that a history of biliary disease was an independent risk factor for ESBL-producing KPLA. Compared with the non-ESBL-producing KPLA group, the ESBL-producing KPLA group had a significantly higher intensive care unit (ICU) admission rate (28.57% vs. 2.33%, p < 0.001). All ESBL-producing KP isolates were susceptible to carbapenems and amikacin. Only the presence of multiloculation on CT was found to be significantly different between the groups (50% vs. 82.56%, p = 0.012).

Conclusions

The presence of biliary disease was an independent risk factor for ESBL-producing KPLA. Patients with ESBL-producing KPLA had a higher ICU admission rate, with only half of patients having evidence of multiloculation on CT.
Imaging features of the initial chest thin-section CT scans from 110 patients after admission with suspected or confirmed diagnosis of COVID-19
Authors: Long Cheng-Juan , Fang Ping , Song Tie-Jun , Zhang Jing-Chao , Yang Qing
Published: June 2020

Background

In December 2019, an outbreak of a novel coronavirus pneumonia, now called COVID-19, occurred in Wuhan, Hubei Province, China. COVID-19, which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread quickly across China and the rest of the world. This study aims to evaluate initial chest thin-section CT findings of COVID-19 patients after their admission at our hospital.

Methods

Retrospective study in a tertiary referral hospital in Anhui, China. From January 22, 2020 to February 16, 2020, 110 suspected or confirmed COVID-19 patients were examined using chest thin-section CT. Patients in group 1 (n = 51) presented with symptoms of COVID-19 according to the diagnostic criteria. Group 2 (n = 29) patients were identified as a high degree of clinical suspicion. Patients in group 3 (n = 30) presented with mild symptoms and normal chest radiographs. The characteristics, positions, and distribution of intrapulmonary lesions were analyzed. Moreover, interstitial lesions, pleural thickening and effusion, lymph node enlargement, and other CT abnormalities were reviewed.

Results

CT abnormalities were found only in groups 1 and 2. The segments involved were mainly distributed in the lower lobes (58.3%) and the peripheral zone (73.8%). The peripheral lesions, adjacent subpleural lesions, accounted for 51.8%. Commonly observed CT patterns were ground-glass opacification (GGO) (with or without consolidation), interlobular septal thickening, and intralobular interstitial thickening. Compared with group 1, patients in group 2 presented with smaller lesions, and all lesions were distributed in fewer lung segments. Localized pleural thickening was observed in 51.0% of group 1 patients and 48.2% of group 2 patients. The prevalence of lymph node enlargement in groups 1 and 2 combined was extremely low (1 of 80 patients), and no significant pleural effusion or pneumothorax was observed (0 of 80 patients).

Conclusion

The common features of chest thin-section CT of COVID-19 are multiple areas of GGO, sometimes accompanied by consolidation. The lesions are mainly distributed in the lower lobes and peripheral zone, and a large proportion of peripheral lesions are accompanied by localized pleural thickening adjacent to the subpleural region.
Repository corticotropin injection versus corticosteroids for protection against renal damage in a focal segmental glomerulosclerosis rodent model
Authors: Hayes Kyle , Warner Elizabeth , Bollinger Chris , Wright Dale , Fitch Richard M.
Published: June 2020

Background

Focal segmental glomerulosclerosis (FSGS) causes renal fibrosis and may lead to kidney failure. FSGS and its common complication, proteinuria, are challenging to treat. Corticosteroids are ineffective in many patients with FSGS, and alternative treatments often yield suboptimal responses. Repository corticotropin injection (RCI; Acthar® Gel), a naturally sourced complex mixture of purified adrenocorticotropic hormone analogs and other pituitary peptides, may have beneficial effects on idiopathic FSGS via melanocortin receptor activation.

Methods

Two studies in a preclinical (female Sprague-Dawley rats) puromycin aminonucleoside FSGS model assessed the effect of RCI on renal function and morphology: an 8-week comparison of a single RCI dose with methylprednisolone (N = 27), and a 12-week chronic RCI dose range study (N = 34). Primary outcomes were proteinuria and renal pathology improvements for measures of renal fibrosis, tubular damage, glomerular injury, and total kidney injury score. Impact of RCI treatment was also determined by assessing urinary biomarkers for renal injury, podocyte expression of podoplanin (a biomarker for injury), podocyte effacement by electron microscopy, and histological staining for fibrosis biomarkers.

Results

Compared with saline treatment, RCI 30 IU/kg significantly reduced proteinuria, with a 38% reduction in peak mean urine protein levels on day 28 in the 8-week model, and RCI 10 IU/kg, 30 IU/kg, and 60 IU/kg reduced peak mean urine protein in the 12-week model by 18, 47, and 44%, respectively. RCI also showed significant dose-dependent improvements in fibrosis, interstitial inflammation, tubular injury, and glomerular changes. Total kidney injury score (calculated from histopathological evaluations) demonstrated statistically significant improvements with RCI 30 IU/kg in the 8-week study and RCI 60 IU/kg in the 12-week study. RCI treatment improved levels of urinary biomarkers of kidney injury (KIM-1 and OPN), expression of podoplanin, and podocyte morphology. RCI also reduced levels of desmin and fibrosis-associated collagen deposition staining. Methylprednisolone did not improve renal function or pathology in this model.

Conclusions

These results provide evidence supporting the improvement of FSGS with RCI, which was superior to corticosteroid treatment in this experimental model. To the authors’ knowledge, this is the first evidence that a drug for the treatment of FSGS supports podocyte recovery after repeated injury.
Congenital thrombotic thrombocytopenic purpura (TTP) with placental abruption despite maternal improvement: a case report
Authors: Soffer Marti D. , Bendapudi Pavan K. , Roberts Drucilla J. , Edelson P. Kaitlyn , Kuter David J. , Ecker Jeffrey L. , Bryant Allison , Goldfarb Ilona T.
Published: June 2020

Background

Thrombotic thrombocytopenic purpura (TTP) is a rare but serious complication in pregnancy that places the mother and fetus at high risk for morbidity and mortality. This case illustrates novel pregnancy complications associated with this rare medical condition.

Case presentation

A 31-year-old G3P0020 at 28 weeks and 1 day was admitted with severe thrombocytopenia and was ultimately diagnosed with TTP. With therapeutic plasma exchange (TPE), maternal status improved. At 28 weeks 6 days, however, non-reassuring fetal testing prompted cesarean delivery with placental abruption noted intraoperatively. Pathology examination confirmed placental abruption and also revealed multiple placental infarcts.

Conclusion

While medical management of TTP can significantly improve the health of the mother, this case highlights the potential role of TTP in abruption and other placental pathology and thus, the need for close fetal surveillance throughout an affected pregnancy.
Altered staining patterns and expression level of Engrailed-2 in benign prostatic hyperplasia and prostate Cancer predict prostatic disease progression
Authors: Li Qi , Shi Yibo , Sa Rigai , Hao Jun , Hu Jinhao , Xiao Mulun , Wang Chaoliang , Yan Liang , Qiao Baoping , Chen Guoxun
Published: June 2020

Background

Prostate cancer (PC), a common malignant tumor, is the second-leading cause of cancer death among American men. Its successful treatment greatly relies on the early diagnose. Engrailed-2 (EN2) has been confirmed being existed with a high level in the urine of PC patients. In this study, to explore the application of EN2 in PC, we detected the immunohistochemical staining difference and EN2 expression level between benign prostatic hyperplasia (BPH) and PC.

Methods

We developed a monoclonal antibody against the helix 3 in EN2 and confirmed its specificity with Western blotting (WB) and immunofluorescence detecting the subcellular localization of endogenous and exogenous EN2 in three PC cell lines (LNCap, PC3, and DU145). We conducted immunohistochemical staining using this homemade antibody, and RT-PCR to detect the expression of EN2 in 25 PC and 25 BPH cases, and analyzed the correlation of EN2 expression and PC clinical staging.

Results

The results of WB and immunofluorescence showed our homemade EN2 monoclonal antibody could specifically bind endogenous and exogenous EN2 protein in three different PC cell lines. Endogenous EN2 was generally expressed in the cytoplasm and exogenous EN2 mostly existed in the nucleus of these cell lines. Immunohistochemical staining in PC had extremely stronger signals than that in BPH, suggesting a higher EN2 expression level in PC, which was confirmed by RT-PCR. Interestingly, the stained areas in BPH tissues were mainly in nucleus and cytoplasm, while in PC tissues were mainly on cytomembrane. Moreover, the expression level of EN2 was positively correlated with the PC clinical staging.

Conclusion

Using our homemade EN2 antibody, we have found different staining patterns and expression level of EN2 in BPH and PC,which may be helpful to predict prostatic disease progression.
Anatomical and functional responses in eyes with diabetic macular edema treated with “1 + PRN” ranibizumab: one-year outcomes in population of mainland China
Authors: Lai Kunbei , Huang Chuangxin , Li Longhui , Gong Yajun , Xu Fabao , Zhong Xiaojing , Lu Lin , Jin Chenjin
Published: June 2020

Background

To evaluate the anatomical and functional responses in eyes with diabetic macular edema (DME) treated with ranibizumab under “1 + pro re nata (PRN)” regimen.

Methods

This prospective interventional case series included 69 eyes of 69 patients with DME treated with intravitreal injections of 0.5 mg ranibizumab followed by repeated injections as needed. Best-corrected visual acuity (BCVA), central foveal thickness (CFT), subfoveal choroidal thickness (SFCT), and predictive factors for final visual outcomes were assessed.

Results

Logarithm of minimal angle of resolution (logMAR) BCVA improved from 0.64 ± 0.23 at baseline to 0.56 ± 0.27, 0.53 ± 0.26, 0.47 ± 0.25, 0.44 ± 0.32, 0.47 ± 0.26 and 0.46 ± 0.26 at time-point of months 1, 2, 3, 6, 9, and 12, respectively (P < 0.05 for any follow-up time-point except month 1). CFT decreased from 478.23 ± 172.31 μm at baseline to 349.74 ± 82.21 μm, 313.52 ± 69.62 μm, 292.59 ± 61.07 μm, 284.67 ± 69.85 μm, 268.33 ± 43.03 μm, and 270.39 ± 49.27 μm at above time-points, respectively (P < 0.05). The number of injections was 6.83 times over 12 months’ follow-up under “1 + PRN” regimen. Multivariate analysis showed that the factors including age, BCVA at baseline, disruption of ellipsoid zone, posterior vitreous detachment (PVD), and vitreomacular traction (VMT) were correlated with the final BCVA.

Conclusions

Intravitreal injections of ranibizumab under “1 + PRN” regimen is a not only effective but also safe way to improve visual acuity of DME patients. And older age, lower baseline BCVA, VMT, and disruption of ellipsoid zone are predictors for final poor BCVA while PVD is a positive predictive factor for good final BCVA.

Trial registration

The trial was registered retrospectively in ClinicalTrials.gov on 2 June 2019 (NCT03973138).