bluuebunny/crossref_metadata_2025 huggingface dataset:
Watershed or bank-to-bank? Scales of governance and the geographic definition of Great Lakes Areas of Concern
Authors: Holifield Ryan , Williams Kathleen C
Published: July 2020

Much recent scholarship has addressed the rise of the watershed as the preferred scale for the governance of water quality. Although the watershed remains widely perceived as an ideal, “natural” scale of freshwater governance, arguments for the merits of alternative scales and multi-scalar approaches are gaining prominence. The Great Lakes Areas of Concern program, managed jointly by the United States and Canada, represents an important case in which the watershed has not prevailed as the default local scale of governance, at least in the 31 Areas of Concern located in the United States or straddling the international border. Based on a review of documents and analysis of a survey and interviews with key actors from local Areas of Concern, we find considerable variation among U.S. states in the designation of Areas of Concern as watersheds and partial watersheds, bank-to-bank watercourse segments, or hybrids of both. This variation depends not only on the differing biophysical conditions at Areas of Concern but also on differences in the latitude that state agencies gave to local stakeholder groups when the geographical extent of each Areas of Concern was designated and negotiated. In several cases, questions about the appropriate scale of the Areas of Concern led to controversy, with implications for subsequent remediation. We contend that understanding the uneven embrace of the watershed as a scale of water governance requires attending not only to specific governance objectives but also to variations in the relationships between local and subnational scales in governance programs.
Assembly of alternative prothrombinase by extracellular histones initiates and disseminates intravascular coagulation
Authors: Abrams Simon T. , Su Dunhao , Sahraoui Yasmina , Lin Ziqi , Cheng Zhenxing , Nesbitt Kate , Alhamdi Yasir , Harrasser Micaela , Du Min , Foley Jonathan H. , Lillicrap David , Wang Guozheng , Toh Cheng-Hock
Published: July 2020

Thrombin generation is pivotal to both physiological blood clot formation and pathological development of disseminated intravascular coagulation (DIC). In critical illness, extensive cell damage can release histones into the circulation, which can increase thrombin generation and cause DIC, but the molecular mechanism is not clear. Typically, thrombin is generated by the prothrombinase complex, comprising activated factor X (FXa), activated cofactor V (FVa), and phospholipids to cleave prothrombin in the presence of calcium. In this study, we found that in the presence of extracellular histones, an alternative prothrombinase could form without FVa and phospholipids. Histones directly bind to prothrombin fragment 1 (F1) and fragment 2 (F2) specifically to facilitate FXa cleavage of prothrombin to release active thrombin, unlike FVa, which requires phospholipid surfaces to anchor the classical prothrombinase complex. In vivo, histone infusion into mice induced DIC, which was significantly abrogated when prothrombin F1 + F2 were infused prior to histones, to act as decoy. In a cohort of intensive care unit patients with sepsis (n = 144), circulating histone levels were significantly elevated in patients with DIC. These data suggest that histone-induced alternative prothrombinase without phospholipid anchorage may disseminate intravascular coagulation and reveal a new molecular mechanism of thrombin generation and DIC development. In addition, histones significantly reduced the requirement for FXa in the coagulation cascade to enable clot formation in factor VIII (FVIII)– and FIX-deficient plasma, as well as in FVIII-deficient mice. In summary, this study highlights a novel mechanism in coagulation with therapeutic potential in both targeting systemic coagulation activation and correcting coagulation factor deficiency.
Molecular disparity in human leukocyte antigens is associated with outcomes in haploidentical stem cell transplantation
Authors: Zou Jun , Ciurea Stefan O. , Kongtim Piyanuch , Yi Min , Carmazzi Yudith , Rondon Gabriela , Srour Samer , Partlow David , Champlin Richard E. , Cao Kai
Published: July 2020

Haploidentical donors are increasingly used for patients requiring hematopoietic stem cell transplantation (HSCT). Although several factors have been associated with transplant outcomes, the impact of HLA disparity in haploidentical HSCT (haplo-HSCT) remains unclear. We investigated the impact of HLA disparity quantified by mismatched eplets (ME) load of each HLA locus on the clinical outcome of 278 consecutive haploidentical transplants. Here, we demonstrated that the degree of HLA molecular mismatches, at individual HLA loci, may be relevant to clinical outcome in the haplo-HSCT. A significantly better overall survival was associated with higher ME load from HLA-A (hazard ratio [HR], 0.97; 95% confidence interval [CI], 0.95-0.99; P = .003) and class I loci (HR, 0.99; 95% CI, 0.97-0.99; P = .045) in the host-versus-graft direction. The apparent survival advantage of HLA-A ME was primarily attributed to reduced risk in relapse associated with an increase in HLA-A ME load (subdistribution HR, 0.95; 95% CI, 0.92-0.98; P = .004). Furthermore, we have identified an association between the risk of grade 3-4 acute graft-versus-host disease (GVHD) and a higher ME load at HLA-B and class I loci in graft-versus-host (GVH) direction. Additionally, GVH nonpermissive HLA-DPB1 mismatch defined by T-cell epitope grouping was significantly associated with relapse protection (subdistribution HR, 0.19; 95% CI, 0.06-0.59; P = .004) without a concurrent increase in GVHD. These findings indicate that alloreactivity generated by HLA disparity at certain HLA loci is associated with transplant outcomes, and ME analysis of individual HLA loci might assist donor selection and risk stratification in haplo-HSCT.
Dynamic Stiffness Analysis and Experimental Verification of Axial Magnetic Bearing Based on Air Gap Flux Variation in Magnetically Suspended Molecular Pump
Authors: Sun Jinji , Wei Wanting , Tang Jiqiang , Wang Chun-E
Published: July 2020

Current and displacement stiffness are important parameters of axial magnetic bearing (AMB) and are usually considered as constants for the control system. However, in actual dynamic work situations, time-varying force leads to time-varying currents and air gap with a specific frequency, which makes the stiffness of appear decrease and even worsens control performance for the whole system. In this paper, an AMB dynamic stiffness model considering the flux variation across the air gap due to frequency is established to obtain the accurate dynamic stiffness. The dynamic stiffness characteristics are analyzed by means of the dynamic equivalent magnetic circuit method. The analytical results show that the amplitude of current and displacement stiffness decreases with frequency increasing. Moreover, compared with the stiffness model without considering the variation of flux density across the air gap, the improved dynamic stiffness results are closer to the actual results. Through the dynamic stiffness measurement method of AMB, experiments of AMB in magnetically suspended molecular pump (MSMP) are carried out and the experimental results are consistent with theoretical analysis results. This paper proposes the dynamic stiffness model of axial magnetic bearing considering the variation of flux density across the air gap, which improves the accuracy of the AMB stiffness analysis.
Firing activity of locus coeruleus noradrenergic neurons decreases in necdin-deficient mice, an animal model of Prader–Willi syndrome
Authors: Wu Rui-Ni , Hung Wei-Chen , Chen Ching-Tsuey , Tsai Li-Ping , Lai Wen-Sung , Min Ming-Yuan , Wong Shi-Bing
Published: July 2020

Background

Prader–Willi syndrome (PWS) is a neurodevelopmental disorder characterized by multiple respiratory, cognitive, endocrine, and behavioral symptoms, such as central apnea, intellectual disabilities, exaggerated stress responses, and temper tantrums. The locus coeruleus noradrenergic system (LC-NE) modulates a diverse range of behaviors, including arousal, learning, pain modulation, and stress-induced negative affective states, which are possibly correlated with the pathogenesis of PWS phenotypes. Therefore, we evaluated the LC-NE neuronal activity of necdin-deficient mice, an animal model of PWS.

Methods

Heterozygous necdin-deficient mice (B6.Cg-Ndntm1ky) were bred from wild-type (WT) females to generate WT (+m/+p) and heterozygotes (+m/−p) animals, which were examined of LC-NE neuronal activity, developmental reflexes, and plethysmography.

Results

On slice electrophysiology, LC-NE neurons of Ndntm1ky mice with necdin deficiency showed significantly decreased spontaneous activities and impaired excitability, which was mediated by enhanced A-type voltage-dependent potassium currents. Ndntm1ky mice also exhibited the neonatal phenotypes of PWS, such as hypotonia and blunt respiratory responses to hypercapnia.

Conclusions

LC-NE neuronal firing activity decreased in necdin-deficient mice, suggesting that LC, the primary source of norepinephrine in the central nervous system, is possibly involved in PWS pathogenesis.
Proteomic approaches for characterizing renal cell carcinoma
Authors: Clark David J. , Zhang Hui
Published: July 2020

Renal cell carcinoma is among the top 15 most commonly diagnosed cancers worldwide, comprising multiple sub-histologies with distinct genomic, proteomic, and clinicopathological features. Proteomic methodologies enable the detection and quantitation of protein profiles associated with the disease state and have been explored to delineate the dysregulated cellular processes associated with renal cell carcinoma. In this review we highlight the reports that employed proteomic technologies to characterize tissue, blood, and urine samples obtained from renal cell carcinoma patients. We describe the proteomic approaches utilized and relate the results of studies in the larger context of renal cell carcinoma biology. Moreover, we discuss some unmet clinical needs and how emerging proteomic approaches can seek to address them. There has been significant progress to characterize the molecular features of renal cell carcinoma; however, despite the large-scale studies that have characterized the genomic and transcriptomic profiles, curative treatments are still elusive. Proteomics facilitates a direct evaluation of the functional modules that drive pathobiology, and the resulting protein profiles would have applications in diagnostics, patient stratification, and identification of novel therapeutic interventions.
Investigating the impact of preselection on subsequent single-step genomic BLUP evaluation of preselected animals
Authors: Jibrila Ibrahim , ten Napel Jan , Vandenplas Jeremie , Veerkamp Roel F. , Calus Mario P. L.
Published: July 2020

Background

Preselection of candidates, hereafter referred to as preselection, is a common practice in breeding programs. Preselection can cause bias and accuracy loss in subsequent pedigree-based best linear unbiased prediction (PBLUP). However, the impact of preselection on subsequent single-step genomic BLUP (ssGBLUP) is not completely clear yet. Therefore, in this study, we investigated, across different heritabilities, the impact of intensity and type of preselection on subsequent ssGBLUP evaluation of preselected animals.

Methods

We simulated a nucleus of a breeding programme, in which a recent population of 15 generations was produced with PBLUP-based selection. In generation 15 of this recent population, the parents of the next generation were preselected using several preselection scenarios. These scenarios were combinations of three intensities of preselection (no, high or very high preselection) and three types of preselection (genomic, parental average or random), across three heritabilities (0.5, 0.3 or 0.1). Following each preselection scenario, a subsequent evaluation was performed using ssGBLUP by excluding all the information from the preculled animals, and these genetic evaluations were compared in terms of accuracy and bias for the preselected animals, and in terms of realized genetic gain.

Results

Type of preselection affected selection accuracy at both preselection and subsequent evaluation stages. While preselection accuracy decreased, accuracy in the subsequent ssGBLUP evaluation increased, from genomic to parent average to random preselection scenarios. Bias was always negligible. Genetic gain decreased from genomic to parent average to random preselection scenarios. Genetic gain also decreased with increasing intensity of preselection, but only by a maximum of 0.1 additive genetic standard deviation from no to very high genomic preselection scenarios.

Conclusions

Using ssGBLUP in subsequent evaluations prevents preselection bias, irrespective of intensity and type of preselection, and heritability. With GPS, in addition to reducing the phenotyping effort considerably, the use of ssGBLUP in subsequent evaluations realizes only a slightly lower genetic gain than that realized without preselection. This is especially the case for traits that are expensive to measure (e.g. feed intake of individual broiler chickens), and traits for which phenotypes can only be measured at advanced stages of life (e.g. litter size in pigs).
An Endostatin-lentivirus (ES-LV)-EPC gene therapy agent for suppression of neovascularization in oxygen-induced retinopathy rat model
Authors: Ai Jing , Ma Jian , Chen Zhi-Qing , Sun Jun-Hui , Yao Ke
Published: July 2020

Background

Transplantation of gene transfected endothelial progenitor cells (EPCs) has provided novel methods for tumor neovascularization therapy but not for ocular disease therapy. This study aimed to investigate the efficacy of endostatin transfected EPCs in retinal neovascularization therapy.

Results

Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) showed the high expression of endostatin in endostatin-lentivirus-EPCs. The neovascularization leakage area and the number of preretinal neovascular cell nuclei were significantly decreased in the endostatin-lentivirus and endostatin-lentivirus-EPC groups, and the effects of these two treatments on inhibiting retinal neovascularization were almost the same. These two groups also showed the greater retinal distribution of endostatin. Intravitreal injections of endostatin-lentivirus-EPCs inhibited retinal neovascularization, vascular endothelial growth factor (VEGF) and CD31 expression, and increased endostatin expression in vivo. Endostatin-lentivirus-EPCs targeted and prevented pathologic retinal neovascularization.

Conclusions

Gene-combined EPCs represent a potential new therapeutic agent for the treatment of neovascular eye diseases.
Evolutionary and developmental considerations of the diet and gut morphology in ceratophryid tadpoles (Anura)
Authors: Fabrezi Marissa , Cruz Julio César
Published: July 2020

Background

Before metamorphosis, almost all anuran tadpoles are omnivores. Larval carnivory occurs in some species and, it is associated with distinctive morphotypes. Obligatory carnivorous tadpoles exhibit structural changes in the gastrointestinal tract compared to larvae that are predominately omnivores. The most distinctive feature of the anuran family Ceratophyridae (three genera) overall is the enormous gape of adults. This feature increases their ability to capture extremely large and active prey. The larvae of Ceratophyrid genera are remarkably distinct from each other and carnivory has diversified in a manner unseen in other anurans. The larvae of one genus, Lepidobatrachus, has a massive gape like the adult. Herein, we report on larval developmental variation, diet, gross morphology of the gastrointestinal tract, and histology of the cranial segment of the gut before, during and after metamorphosis in larval series for the following ceratophryid species: Chacophrys pierottii, Ceratophrys cranwelli, Lepidobatrachus laevis and Lepidobatrachus llanensis.

Results

We described patterns of larval development with variation in growth with consequence to the final size at the end of metamorphosis. These patterns seem to be influenced by food quantity/quality, and most predominant by animal protein. Prey items found in pre and post-metamorphic Lepidobatrachus spp. are similar. Tadpoles of Ceratophrys and Chacophrys (and other anurans) share a short cranial segment of the gut with an internal glandular, mucous secreting epithelium, a double coiled intestine and the sequence of metamorphic changes (tract is empty, the stomach differentiates and the intestine shortens abruptly). In contrast, Lepidobatrachus tadpoles have a true stomach that acquires thickness and increased glandular complexity through development. As larvae they have a short intestine without double coils, and the absence of intestine shortening during metamorphosis.

Conclusions

The larval development of the gastrointestinal tract of Lepidobatrachus is unique compared with that of other free-living anuran larvae. An abrupt metamorphic transformation is missing and most of the adult structural features start to differentiate gradually at the beginning of larval stages.
A concept analysis of dignity-protective continence care for care dependent older people in long-term care settings
Authors: Ostaszkiewicz Joan , Dickson-Swift Virginia , Hutchinson Alison , Wagg Adrian
Published: July 2020

Background

Although codes of conduct, guidelines and standards call for healthcare practitioners to protect patients’ dignity, there are widespread concerns about a lack of attention to the dignity of older people who need assistance with toileting, incontinence or bladder or bowel care in health or social care settings that provide long-term care. Incontinence and care dependence threatens patient dignity. The aim of this research was to explore, describe and explain the concept of dignity as it relates to continence care for older people requiring long-term care.

Methods

The first four steps of Rodgers evolutionary method of concept analysis were followed. First, a comprehensive and systematic search of databases and key guidelines about continence care was undertaken to identify empirical research about dignity and continence care in older people in facilities that provide permanent residential or inpatient care of older people for day-to-day living. Data were extracted on the authors, date, sample, country of origin, and key definitions, attributes, contexts and consequences from each included record. Findings were inductively analysed and grouped according to whether they were the key attributes and antecedents of dignity in relation to continence care or the consequences of undignified continence care.

Results

Of 625 articles identified, 18 were included in the final analysis. Fifty individual attributes were identified that were categorised in 6 domains (respect, empathy, trust, privacy, autonomy and communication). A further 15 were identified that related to the environment (6 physical and 9 social). Key consequences of undignified continence care were also identified and categorised into 3 levels of impact (resident/family member, staff or organisation).

Conclusions

This research resulted in a conceptual understanding of dignity that can be used as a value or guiding principle in an ethic of care for older people who need assistance with toileting, incontinence or bladder or bowel care in long-term care settings.
Clinical, biochemical, and genetic analysis of a Chinese Han pedigree with holocarboxylase synthetase deficiency: a case report
Authors: Zheng Zhenzhu , Yuan Gaopin , Zheng Minyan , Lin Yiming , Zheng Faming , Jiang Mengyi , Zhu Lin , Fu Qingliu
Published: July 2020

Background

Holocarboxylase synthetase (HLCS) deficiency is a rare inborn disorder of biotin metabolism, which results in defects in several biotin-dependent carboxylases and presents with metabolic ketoacidosis and skin lesions.

Case presentation

In this paper, we report a Chinese Han pedigree with HLCS deficiency diagnosed by using next-generation sequencing and validated with Sanger sequencing of the HLCS and BTD genes. The Chinese proband carries the common missense mutation c.1522C > T (p.Arg508Trp) in exon 9 of the HLCS gene, which generates an increased Km value for biotin. A novel frameshift mutation c.1006_1007delGA (p.Glu336Thrfs*15) in exon 6 of the HLCS gene is predicted to be deleterious through PROVEAN and MutationTaster. A novel heterozygous mutation, c.638_642delAACAC (p.His213Profs*4), in the BTD gene is also identified.

Conclusions

The Chinese proband carries the reported Arg508Trp variant, the novel 2-bp frameshift mutation c.1006_1007delGA (p.Glu336Thrfs*15), which expands the mutational spectrum of the HLCS gene, and the novel heterozygous mutation c.638_642delAACAC (p.His213Profs*4), which expands the mutational spectrum of the BTD gene. Furthermore, reversible hearing damage is rarely reported in patients with HLCS deficiency, which deserves further discussion.
Assessment of the results and hematological side effects of 3D conformal and IMRT/ARC therapies delivered during craniospinal irradiation of childhood tumors with a follow-up period of five years
Authors: Lőcsei Zoltán , Farkas Róbert , Borbásné Farkas Kornélia , Sebestyén Klára , Sebestyén Zsolt , Musch Zoltán , Vojcek Ágnes , Benedek Noémi , Mangel László , Ottóffy Gábor
Published: July 2020

Background

Craniospinal irradiation (CSI) of childhood tumors with the RapidArc technique is a new method of treatment. Our objective was to compare the acute hematological toxicity pattern during 3D conformal radiotherapy with the application of the novel technique.

Methods

Data from patients treated between 2007 and 2014 were collected, and seven patients were identified in both treatment groups. After establishing a general linear model, acute blood toxicity results were obtained using SPSS software. Furthermore, the exposure dose of the organs at risk was compared. Patients were followed for a minimum of 5 years, and progression-free survival and overall survival data were assessed.

Results

After assessment of the laboratory parameters in the two groups, it may be concluded that no significant differences were detected in terms of the mean dose exposures of the normal tissues or the acute hematological side effects during the IMRT/ARC and 3D conformal treatments. Laboratory parameters decreased significantly compared to the baseline values during the treatment weeks. Nevertheless, no significant differences were detected between the two groups. No remarkable differences were confirmed between the two groups regarding the five-year progression-free survival or overall survival, and no signs of serious organ toxicity due to irradiation were observed during the follow-up period in either of the groups.

Conclusion

The RapidArc technique can be used safely even in the treatment of childhood tumors, as the extent of the exposure dose in normal tissues and the amount of acute hematological side effects are not higher with this technique.
Clinical characteristics of hyperprogressive disease in NSCLC after treatment with immune checkpoint inhibitor: a systematic review and meta-analysis
Authors: Chen Yan , Hu Junjie , Bu Fangfang , Zhang Haiping , Fei Ke , Zhang Peng
Published: July 2020

Background

A number of studies have reported hyperprogressive disease (HPD) in non-small cell lung cancer (NSCLC) after treatment with immune checkpoint inhibitor (ICI). This study aimed to summarize the incidence and survival outcome of HPD in NSCLC and identify the clinicopathological features associated with HPD based on available eligible studies.

Methods

Four databases (Medline/PubMed, Embase, Web of Science, and Cochrane Library) were searched for eligible studies on HPD published before January 23, 2020, to evaluate the incidence, outcome, and clinical features of HPD. Statistical analyses were performed using STATA 15.0. All meta-analyses were performed based on the random-effects model.

Results

This study included 6 studies involving 1389 patients. The incidence of HPD ranged from 8.02 to 30.43%. Compared with patients with non-HPD, those with HPD were associated with worse overall survival. We identified that Eastern Cooperative Oncology Group > 1, Royal Marsden Hospital score ≥ 2, serum lactate dehydrogenase > upper limit of normal, the number of metastasis sites > 2, and liver metastasis were associated with the risk of HPD.

Conclusions

This study summarized the clinical features of HPD in NSCLC patients. The meta-analysis showed that five pre-treatment clinicopathological features might be associated with HPD, which may help in selecting patients for ICIs.
Trends in the prevalence of twenty health indicators among adolescents in United Arab Emirates: cross-sectional national school surveys from 2005, 2010 and 2016
Authors: Pengpid Supa , Peltzer Karl
Published: July 2020

Background

The aim of this study was to assess the trends in the prevalence of various health indicators among adolescents in United Arab Emirates (UAE).

Methods

Nationally representative data were analysed from 24,220 in-school adolescents (median age = 14 years) that took part in three cross-sectional surveys (2005, 2010 and 2016) of the “UAE Global School-Based Student Health Survey (GSHS)”.

Results

Significant improvements were identified among both girls and boys in the reduction of being physically attacked, inadequate fruit intake, inadequate vegetable consumption, loneliness, and among girls only poor oral hygiene (< 2 times tooth brushing/day) and among boys only, experiencing hunger and in physical fight. Significant rises were identified among both girls and boys in the prevalence of bullying victimization, overweight or obesity, leisure-time sedentary behaviour, injury and inconsistent washing hands prior to eating, and among boys only obesity and among girls only inadequate physical activity, and school truancy.

Conclusions

Several reductions but even more increases of poor health indicators were identified over three cross-sectional surveys during a period of 11 years emphasizing the need for enhanced health promotion activities in this adolescent school population.
Mid-upper arm circumference as an indicator of underweight in adults: a cross-sectional study from Nepal
Authors: Thorup Lene , Hamann Sophie Amalie , Kallestrup Per , Hjortdal Vibeke Elisabeth , Tripathee Ashish , Neupane Dinesh , Patsche Cecilie Blenstrup
Published: July 2020

Background

Undernourished people have an increased risk of premature mortality from both infectious and non-communicable diseases. Aside from screening purposes, assessment of nutritional status is a useful tool in management and evaluation of various chronic diseases. Body-Mass-Index (BMI) is today the most commonly used marker of nutritional status however, this method presents a challenge in many low resource settings and immobile patients. Mid-upper arm circumference (MUAC) is another anthropometric measure that requires minimal equipment and little training. So far, MUAC cutoffs for undernutrition are well established in children < 5 years but there is still no consensus for a specific cutoff in adults. The objective of this study was to compare MUAC with BMI and suggest a MUAC cut-off corresponding to a BMI of 18.5 kg/m2 to identify underweight in adults.

Methods

A cross-sectional study was conducted at two urban public hospitals in Nepal. The following variables where collected: MUAC, weight, height, sex, age and self-reported medical history. Exclusion criteria: < 19 years of age, pregnancy and oedema. Sensitivity and specificity for a MUAC value corresponding to BMI < 18.5 was calculated. ROC analysis was performed for male and female as well as Pearson’s correlation of MUAC and BMI.

Results

A total of 302 people between 18 and 86 years of age, 197 women and 105 men, were included. Of these, 90 people suffered from rheumatic heart disease. MUAC was highly correlated with BMI in both women r = 0.889 and men r = 0.846. Best statistically derived MUAC cutoff corresponding to a BMI < 18.5 kg/m2 was 24.5 cm (Youdens Index = 0.75; sensitivity 92.86; specificity 82.48), with high predictive value (AUROCC> 0.9). The setting based optimal MUAC cutoff was also 24.5 cm. No considerable variation was found in sex- and disease specific subgroups.

Conclusion

MUAC is strongly correlated with BMI in adults in Nepal. For simplicity, a MUAC of 24.5 cm is the optimal statistically and setting based cutoff in both women and men to identify underweight (BMI < 18.5 kg/m2).
Prevalence and risk indicators of non-carious cervical lesions in male footballers
Authors: Medeiros Tamea Lacerda Monteiro , Mutran Sheila Cristina Almeida Neves , Espinosa Daybelis González , do Carmo Freitas Faial Kelson , Pinheiro Helder Henrique Costa , D’Almeida Couto Roberta Souza
Published: July 2020

Background

Non-carious cervical lesions (NCCLs) have shown a significant incidence and prevalence and have been increasingly associated with people’s lifestyles and youths. This cross-sectional study aimed to determine the prevalence of NCCLs in footballers and to address potential risk indicators.

Methods

Fourty-three male semi-professional footballers with an average of 27 years old completed a questionnaire and were subjected to intraoral examination in terms of cervical tooth wear, morphological characteristics of NCCLs, tooth sensitivity, occlusal/incisal wear, and malocclusion classification. Also, laboratory assays were performed to determine salivary parameters: flow rate, pH, buffer capacity, level of Ca (calcium), Na (sodium), and K (potassium) ions, and level of cortisol. The data obtained from the questionnaire and intraoral examinations were subjected to Chi-square and Poisson regression models while the data obtained from the laboratory assays were analyzed by using analysis of variance (p <  0.05).

Results

The prevalence of NCCLs was 39.5%. The participants presented predominantly initial lesions with signs of mechanical stress. The daily training time was found as a significant risk indicator (p = 0.028). The multivariate analysis showed a significant difference in the variables daily training time (p = 0.023), lemon water intake while fasting (p = 0.002), toothpaste type (p = 0.004), tooth sensitivity (p = 0.006); previous orthodontic treatment (p = 0.003), and occlusion type (p = 0.008). All participants presented normal salivary parameters and levels of cortisol.

Conclusion

The prevalence of NCCLs among footballers was remarkable. The premolars were the most affected teeth and presented symptoms/signs of initial lesions. The daily training time was a dominant risk indicator of NCCLs development. Footballers presented adequate salivary parameters and cortisol levels.
Analysis of real-world data on growth hormone therapy adherence using a connected injection device
Authors: Koledova Ekaterina , Tornincasa Vincenzo , van Dommelen Paula
Published: July 2020

Background

Poor adherence to long-term recombinant human growth hormone (r-hGH) treatment can lead to suboptimal clinical outcomes; consequently, supporting and monitoring adherence is a crucial part of patient management. We assessed adherence to r-hGH treatment in children with growth disorders over 48 months using a connected monitoring device (easypod™), which automatically transmits adherence data via an online portal (easypod™ connect); both sit within an adherence decision support system (ADSS). We also investigated the effect of age and sex on adherence.

Methods

Data from children transmitting over 10 injections between January 2007 and February 2019 were analyzed. Adherence (mg injected/mg prescribed) was categorized as high (≥85%), intermediate (> 56–84%) or low (≤56%) and assessed at seven time points from the start of treatment up to 48 months. Adherence was investigated over time and stratified by puberty status and sex. Mean transmission rate in each adherence category (total number of transmissions/total number of children) at each time point was calculated as a proxy measure of engagement in disease and treatment management. Descriptive analyses were performed.

Results

Longitudinal records were available for 13,553 children. Overall, 71% (n = 9578) had high adherence, 22% (n = 2989) intermediate and 7% (n = 986) low. The proportion of children with high adherence decreased over time from 87% (n = 12,964) to 65% (n = 957) and was higher in pre-pubertal than pubertal children (girls: 80% [n = 1270] vs 70% [n = 4496]; boys 79% [n = 2573] vs 65% [n = 5214]). Children with high adherence had a higher mean number of transmissions (12.5 [SD 24.9]) than children with intermediate (7.2 [SD 15.3]) or low (3.5 [SD 5.7]) adherence.

Conclusions

High adherence was seen in patients administering r-hGH using the connected device. Children with high adherence were most likely to regularly transmit data. Pubertal children showed lower adherence. We show the potential to develop an ADSS to analyze trends in real-world adherence data. This may prove useful to direct interventions to improve adherence while the ability to readily share data with healthcare professionals may itself improve adherence.
Challenges of implementing the accreditation model in military and university hospitals in Iran: a qualitative study
Authors: Vali Leila , Mehrolhasani Mohammad Hossein , Mirzaei Saeid , Oroomiei Nadia
Published: July 2020

Background

The aim of this study was to present challenges of implementing the accreditation model in university and military hospitals in Iran.

Methods

In this qualitative study, purposive sampling was used to select hospital managers and implementers of the model working in 3 hospitals affiliated to Kerman University of Medical Sciences and in 3 military hospitals in Kerman, Iran. A total of 39 participants were interviewed, and semi-structured questionnaires and thematic analysis were used for data collection and analysis, respectively.

Results

In this study, 5 major codes and 17 subcodes were identified: (1) perspectives on accreditation model with 5 subcodes: a difficult and time-consuming model, less attention to the patient, accreditation as a way of money acquisition, not being cost-effective, and accreditation means incorrect documentation; (2) absence of appropriate executive policy, with 3 subcodes: lack of financial funds and personnel, disregarding local conditions in implementation and evaluation, and absence of the principle of unity of command; (3) training problems of the accreditation model, with 2 subcodes: absence of proper training and incoordination of training and evaluation; (4) human resources problems, with 3 subcodes: no profit for nonphysician personnel, heavy workload of the personnel, and physicians’ nonparticipation; (5) evaluation problems, with 4 subcodes: no precise and comprehensive evaluation, inconformity of authorities’ perspectives on evaluation, considerable change in evaluation criteria, and excessive reliance on certificates.

Conclusions

This study provided useful data on the challenges of implementing hospitals’ accreditation, which can be used by health policymakers to revise and modify accreditation procedures in Iran and other countries with similar conditions. The accreditation model is comprehensive and has been implemented to improve the quality of services and patients’ safety. The basic philosophy of hospital accreditation did not fully comply with the underlying conditions of the hospitals. The hospital staff considered accreditation as the ultimate goal rather than a means for achieving quality of service. The Ministry of Health and Medical Education performed accreditation hastily for all Iranian hospitals, while the hospitals were not prepared and equipped to implement the accreditation model.
Motivation factors affecting the job attitude of medical doctors and the organizational performance of public hospitals in Warsaw, Poland
Authors: Chmielewska Malgorzata , Stokwiszewski Jakub , Filip Justyna , Hermanowski Tomasz
Published: July 2020

Background

This paper examines the relationship between selected motivation factors that affect the attitude to work among medical doctors at public hospitals and the organizational performance of hospitals.

Methods

This study was based on World Health Organization questionnaires designed to estimate motivation factors according to Herzberg’s motivation theory and to measure the level of organizational performance of hospitals by using the McKinsey model. A survey was conducted among physicians (n = 249) with either surgical (operative) or nonsurgical (conservative) specialty in 22 departments/units of general public hospitals in Warsaw, Poland.

The relationship between the chosen job motivation factors and organizational effectiveness was determined using Spearman’s rank correlation. Furthermore, 95% confidence intervals were calculated. The independent samples t-test was used to confirm statistically significant differences between the independent groups. Normality of the data was tested by the Kolmogorov–Smirnov test.

Results

The survey revealed that motivation factors related to “quality and style of supervision” have the highest effect on the organizational performance of hospitals (Spearman’s rank correlation coefficient = 0.490; p < 0.001), whereas “performance feedback” has the lowest effect on organizational performance according to the surveyed healthcare professionals (54% of physicians).

Conclusion

The principles of Individual Performance Review should be incorporated into strategies designed to improve the organizational performance of hospitals (with NHS serving as a potential role model) in order to establish specific rules on how to share performance feedback with individual physicians. The present study contributes to literature on human resource management in the healthcare sector and highlights the importance of nonfinancial aspects in improving the organizational performance of hospitals.
Interstitial changes after reperfused myocardial infarction in swine: morphometric and genetic analysis
Authors: Rios-Navarro Cesar , Ortega Maria , Marcos-Garces Victor , Gavara Jose , de Dios Elena , Perez-Sole Nerea , Chorro Francisco J. , Bodi Vicente , Ruiz-Sauri Amparo
Published: July 2020

Background

Following myocardial infarction (MI), we aimed to characterize morphometric and genetic changes in extracellular matrix (ECM) components from ischemia onset until late phases after coronary reperfusion in necrotic and salvaged myocardium.

Results

Swine were divided into one control (n = 5) and three MI groups: 90-min of ischemia without reperfusion, or followed by 1-week or 1-month reperfusion (n = 5 per group). In samples from the necrotic and salvaged areas, ECM components were morphometrically quantified and mRNA levels of factors involved in ECM remodeling were evaluated. After 90-min of ischemia, fibronectin, laminin, and elastic fibers content as well as upregulated mRNA expression of tissue inhibitors of metalloproteinases (TIMP)1, TIMP2, TIMP3 and connective tissue growth factor increased in the necrotic and salvaged myocardium. In both reperfused MI groups, collagen-I, collagen-III, elastic fibers, glycosaminoglycans, laminin, and fibronectin levels heightened in the necrotic but not the salvaged myocardium. Moreover, mRNA expression of TIMP1, TIMP2 and TIMP3, as well as metalloproteinase-2 and metalloproteinase-9 heightened in the necrotic but not in the salvaged myocardium.

Conclusions

Matrix remodeling starts after ischemia onset in both necrotic and salvaged myocardium. Even if ECM composition from the salvaged myocardium was altered after severe ischemia, ECM makes a full recovery to normal composition after reperfusion. Therefore, rapid coronary reperfusion is essential not only to save cardiomyocytes but also to preserve matrix, thus avoiding impaired left ventricular remodeling.
Detection of leukemia gene fusions by targeted RNA-sequencing in routine diagnostics
Authors: Engvall Marie , Cahill Nicola , Jonsson Britt-Inger , Höglund Martin , Hallböök Helene , Cavelier Lucia
Published: July 2020

Background

We have evaluated an NGS-based method to detect recurrent gene fusions of diagnostic and prognostic importance in hematological malignancies. Our goal was to achieve a highly specific assay with a simple workflow, short turnaround time and low cost.

Method

The assay uses a commercially available anchored multiplex PCR panel for target enrichment and library preparation, followed by sequencing using a MiSeq instrument. The panel includes all recurrent gene fusions in AML and ALL and is designed to detect gene-specific fusions without prior knowledge of the partner sequence or specific break points. Diagnostic RNA samples from 27 cases with hematological malignancies encompassing 23 different transcript variants were analyzed. In addition, 12 cases from a validation cohort were assessed.

Result

All known fusion transcripts were identified with a high degree of confidence, with a large number of reads covering the breakpoints. Importantly, we could identify gene fusions where conventional methods had failed due to cryptic rearrangements or rare fusion partners. The newly-identified fusion partners were verified by RT-PCR and transcript-specific qPCR was designed for patient-specific follow-up. In addition, 12 cases were correctly assessed in a blind test, without prior knowledge of molecular cytogenetics or diagnosis.

Conclusion

In summary, our results demonstrate that targeted RNA sequencing using anchored multiplex PCR can be implemented in a clinical laboratory for the detection of recurrent and rare gene fusions in hematological diagnostic samples.
The adipokine fatty-acid binding protein 4 and cardiac remodeling
Authors: von Jeinsen Beatrice , Ritzen Lisa , Vietheer Julia , Unbehaun Claudia , Weferling Maren , Liebetrau Christoph , Hamm Christian W. , Rolf Andreas , Keller Till
Published: July 2020

Background

Previous publications about the association between fatty-acid binding protein 4 (FABP4) and cardiac remodeling have reported different, both beneficial and harmful, associations. Aim of the present investigation was to evaluate the association of FABP4 with parameters of myocardial remodeling defined by cardiac magnetic resonance imaging (CMR).

Methods

We investigated plasma FABP4 levels in 331 patients (71% men, mean age 63±13 years) with preserved left ventricular ejection fraction (LVEF ≥ 55%) who underwent a CMR examination. We used linear cox regression to investigate associations between FABP4 and left ventricular end-diastolic diameter (LVEDD), right ventricular end-diastolic diameter (RVEDD), relative wall thickness (RWT), left ventricular mass index (LVMI), and LVEF (unadjusted and adjusted for age, sex, body mass index, cardiac biomarkers, and comorbidities).

Results

FABP4 levels were associated with lower LVMI and higher NT-proBNP levels in an adjusted model. The inverse association between FABP4 and LVMI was more pronounced in lower FABP4 levels, whereas the positive association between FABP4 and NT-proBNP was more pronounced in relatively high NT-proBNP levels.

Conclusions

Possible beneficial and harmful associations between FABP4 and left ventricular size have been reported. Our results suggest a beneficial association with LVMI (more pronounced in lower FABP4 levels) but a harmful association with NT-proBNP (more pronounced in higher FABP4 levels). Therefore, our results might indicate a potential dose-dependent association of FABP4, but this observation needs further investigation in larger study samples.
The length of ribosomal binding site spacer sequence controls the production yield for intracellular and secreted proteins by Bacillus subtilis
Authors: Volkenborn Kristina , Kuschmierz Laura , Benz Nuka , Lenz Patrick , Knapp Andreas , Jaeger Karl-Erich
Published: July 2020

Background

Bacillus subtilis is widely used for the industrial production of recombinant proteins, mainly due to its high secretion capacity, but higher production yields can be achieved only if bottlenecks are removed. To this end, a crucial process is translation initiation which takes place at the ribosome binding site enclosing the Shine Dalgarno sequence, the start codon of the target gene and a short spacer sequence in between. Here, we have studied the effects of varying spacer sequence lengths in vivo on the production yield of different intra- and extracellular proteins.

Results

The shuttle vector pBSMul1 containing the strong constitutive promoter PHpaII and the optimal Shine Dalgarno sequence TAAGGAGG was used as a template to construct a series of vectors with spacer lengths varying from 4 to 12 adenosines. For the intracellular proteins GFPmut3 and β-glucuronidase, an increase of spacer lengths from 4 to 7–9 nucleotides resulted in a gradual increase of product yields up to 27-fold reaching a plateau for even longer spacers. The production of secreted proteins was tested with cutinase Cut and swollenin EXLX1 which were N-terminally fused to one of the Sec-dependent signal peptides SPPel, SPEpr or SPBsn. Again, longer spacer sequences resulted in up to tenfold increased yields of extracellular proteins. Fusions with signal peptides SPPel or SPBsn revealed the highest production yields with spacers of 7–10nt length. Remarkably, fusions with SPEpr resulted in a twofold lower production yield with 6 or 7nt spacers reaching a maximum with 10–12nt spacers. This pattern was observed for both secreted proteins fused to SPEpr indicating a dominant role also of the nucleotide sequence encoding the respective signal peptide for translation initiation. This conclusion was corroborated by RT qPCR revealing only slightly different amounts of transcript. Also, the effect of a putative alternative translation initiation site could be ruled out.

Conclusion

Our results confirm the importance of the 5′ end sequence of a target gene for translation initiation. Optimizing production yields thus may require screenings for optimal spacer sequence lengths. In case of secreted proteins, the 5′ sequence encoding the signal peptide for Sec-depended secretion should also be considered.
Constructing a novel expression system by specific activation of amylase expression pathway in Penicillium
Authors: Pi Changyu , Zhang Zhe , Xiang Boyu , Tian Hongwei , Liao Qinzhen , Chen Yu , Xia Liqiu , Hu Yibo , Hu Shengbiao
Published: July 2020

Background

Filamentous fungi have long been used as hosts for the production of proteins, enzymes and valuable products in various biotechnological applications. However, recombinant proteins are expressed with highly secreted host proteins when stronger promoters are used under inducing conditions. In addition, the efficiency of target protein expression can be limited by the application of constitutive promoters in recently developed filamentous fungal expression systems.

Results

In this study, a novel expression system was constructed by using a Penicillium oxalium strain that has powerful protein secretion capability. The secretory background of the host was reduced by knocking out the Amy13A protein and utilizing the starch as a carbon source. The strong promoter amy15A(p) was further improved by overexpressing the transcription activator AmyR and deleting of putative repressor CreA. By using the native amylase Amy15A as a reporter, the efficiency of expression from the amy15A promoter was dramatically and specifically enhanced after redesigning the regulatory network of amylase expression.

Conclusions

Our researches clearly indicated that the triple-gene recombinant strain Δ13A-OamyR-ΔCreA, with the amy15A(p) promoter could be used as a suitable expression system especially for high-level and high-purity protein production.