bluuebunny/crossref_metadata_2025 huggingface dataset:
Normative reference ranges for echocardiographic chamber dimensions in a healthy Central European population: results from the Czech post-MONICA survey
Authors: Marek Josef , Lubanda Jean-Claude , Cifkova Renata , Kuchynka Petr , Golan Lubor , Nemcek Eduard , Linhart Ales
Published: October 2019

Background

Normative reference values for echocardiographic chamber quantification are of great importance; however, this can be challenging. Our aim was to derive these values including degrees of abnormality from a random Central European population sample with a homogeneous subset of healthy subjects.

Methods

We analysed echocardiograms obtained in a randomly selected population sample during the Czech post-MONICA survey in 2007/2008. Overall, 1850 out of 2273 persons of the whole sample of three districts had adequate echocardiograms (81.4%). A healthy subgroup defined by the absence of known cardiovascular disease was used to define normal reference range limits (n = 575, median age 42 years [IQR 34–52], 57% females). The whole population sample with predefined percentile cut-offs was used to define degrees of abnormality.

Results

Left ventricular (LV) size tended to decrease with age, while LV mass increased with age in both males and females and in both the healthy and general populations. LV dimensions were larger in males, except for body surface area-indexed LV diameter. M-mode derived LV measurements were larger and LV mass higher compared to 2D measurements. Right ventricle basal dimension was larger in males.

Conclusions

Our study provides reference ranges for echocardiographic measurements obtained in a healthy subgroup derived from an epidemiological study of a Central European population. Where feasible, degrees of abnormality are provided based on the whole population sample including patients with disease. Our data show that age, gender and measurement method significantly affect cardiac dimensions and function and should be always taken into account.
Content validity of a novel patient-reported and observer-reported outcomes assessment to evaluate ocular symptoms associated with infectious conjunctivitis in both adult and pediatric populations
Authors: Sarda Sujata P. , De La Cruz Marie , Flood Emuella M. , Vanya Magdalena , Hwang David G. , Ta Christopher N. , Narvekar Abhijit
Published: October 2019

Background

Acute infectious conjunctivitis is a common condition most frequently caused by viruses or bacteria. Clinical outcome assessments have been used to assess signs and symptoms of bacterial and viral conjunctivitis, but have not been evaluated for content validity. We aimed to develop content-valid patient- (PRO) and observer-reported outcome (ObsRO) instruments to assess symptoms of ocular discomfort associated with viral or bacterial conjunctivitis in adult and pediatric patients.

Methods

Draft items were developed from a previous review of published studies from 2001 to 2015. Patients and caregivers of patients with a diagnosis of viral or bacterial conjunctivitis within the past 6 months were recruited. Concept elicitation with open-ended questions explored signs and symptoms, followed by cognitive interviewing to assess clarity and relevance of the draft items. Patients aged ≥8 years were interviewed for the PRO; parents/caregivers of children aged 1–10 years were interviewed for the ObsRO. Interviews were conducted in three rounds to allow changes. Concept saturation was documented using a saturation grid. Cognitive interview data were analyzed iteratively and focused on clarity, relevance and inconsistent interpretation of the instrument’s content.

Results

Overall, 23 patients or parents/caregivers participated (round 1, n = 10; round 2, n = 6; round 3, n = 7). Data saturation was reached by the 16th interview. The most frequent spontaneously reported signs/symptoms were: discharge, red/pink eyes, itchiness, swelling/puffiness, watery eyes, pain, burning and foreign body sensation. Itching, pain/burning/stinging and foreign body sensation were most commonly reported as the top three most bothersome symptoms. Interview results indicated that items on pain, itching and foreign body sensation for the PRO and pain or discomfort for the ObsRO were relevant to the patients’ experience of conjunctivitis and were clear and easy to understand.

Conclusions

PRO and ObsRO items were found to be clear, relevant and appropriate in assessing key viral and bacterial conjunctivitis symptoms in adult and pediatric patients.
EQ-5D-5L utilities per health states in Spanish population with knee or hip osteoarthritis
Authors: García-Pérez Lidia , Ramos-García Vanesa , Serrano-Aguilar Pedro , Pais-Brito José Luis , Aciego de Mendoza María , Martín-Fernández Jesús , García-Maroto Roberto , Arenaza Juan Carlos , Bilbao Amaia
Published: October 2019

Background

The objective of this study was to obtain utilities by means of EQ-5D-5L for different health states in patients with knee osteoarthritis (KOA) or hip osteoarthritis (HOA) in Spain, and to compare these values with those used in foreign studies with the aim of discussing their transferability for their use in economic evaluations conducted in Spain.

Methods

Primary study: Observational prospective study of KOA or HOA patients in Spain. Sociodemographic and clinical characteristics were collected to characterize the sample. Utilities were elicited using the EQ-5D-5L questionnaire. ANOVA and bivariable analyses were conducted to identify differences between health states. Literature review: Using the bibliographic databases NSH EED and CEA Registry, we conducted searches of model-based cost utilities analyses of technologies in KOA or HOA patients. Health states and utilities were extracted and compared with values obtained from the Spanish sample.

Results

Three hundred ninety-seven subjects with KOA and 361 subjects with HOA were included, with average utilities of 0.544 and 0.520, respectively. In both samples, differences were found in utilities according to level of pain, stiffness and physical function (WOMAC) and severity of symptoms (Oxford scales), so that the worst the symptoms, the lower the utilities. The utilities after surgery were higher than before surgery. Due to limitations from our study related to sample size and observational design, it was not possible to estimate utilities for approximately half the health states included in the published models because they were directly related to specific technologies. For almost 100% of health states of the selected studies we obtained very different utilities from those reported in the literature.

Conclusions

To our knowledge this is the first article with detailed utilities estimated using the EQ-5D-5L in Spain for KOA and HOA patients. In both populations, utilities are lower for worse health states in terms of level of pain, stiffness and physical function according to WOMAC, and according to the Oxford scales. Most utilities obtained from the Spanish sample are lower than those reported in the international literature. Further studies estimating utilities from local populations are required to avoid the use of foreign sources in economic evaluations.
Flipping the dogma – phosphatidylserine in non-apoptotic cell death
Authors: Shlomovitz Inbar , Speir Mary , Gerlic Motti
Published: October 2019

The exposure of phosphatidylserine (PS) on the outer plasma membrane has long been considered a unique feature of apoptotic cells. Together with other “eat me” signals, it enables the recognition and phagocytosis of dying cells (efferocytosis), helping to explain the immunologically-silent nature of apoptosis. Recently, however, PS exposure has also been reported in non-apoptotic forms of regulated inflammatory cell death, such as necroptosis, challenging previous dogma. In this review, we outline the evidence for PS exposure in non-apoptotic cells and extracellular vesicles (EVs), and discuss possible mechanisms based on our knowledge of apoptotic-PS exposure. In addition, we examine the outcomes of non-apoptotic PS exposure, including the reversibility of cell death, efferocytosis, and consequent inflammation. By examining PS biology, we challenge the established approach of distinguishing apoptosis from other cell death pathways by AnnexinV staining of PS externalization. Finally, we re-evaluate how PS exposure is thought to define apoptosis as an immunologically silent process distinct from other non-apoptotic and inflammatory cell death pathways. Ultimately, we suggest that a complete understanding of how regulated cell death processes affect the immune system is far from being fully elucidated.

Graphical abstract
Analysis of prognosis, genome, microbiome, and microbial metabolome in different sites of colorectal cancer
Authors: Xi Yang , Yuefen Pan , Wei Wu , Quan Qi , Jing Zhuang , Jiamin Xu , Shuwen Han
Published: October 2019

Background

The colorectum includes ascending colon, transverse colon, descending colon, sigmoid colon, and rectum. Different sites of colorectal cancer (CRC) are different in many aspects, including clinical symptoms, biological behaviour, and prognosis.

Purpose

This study aimed to analyse prognosis, genes, bacteria, fungi, and microbial metabolome in different sites of CRC.

Methods

The Surveillance, Epidemiology, and End Results (SEER) database and STAT were used to statistically describe and analyse the prognosis in different sites of CRC. RNA sequences of CRC from Broad Institute’s GDAC Firehose were re-annotated and reanalysed based on different sites using weighted gene co-expression network analysis (WGCNA). The Kaplan–Meier method was used to analyse the prognosis and Cytoscape was used to construct a drug-target network based on DGIdb databases. Bacterial 16S V3–V4 and fungal ITS V3–V4 ribosomal RNA genes of stool samples were sequenced. Gas chromatography/mass spectrometry (GS/MS) was performed to detect the microbial metabolites in stool samples. Bioinformatics analysis was performed to compare distinct gut microorganisms and microbial metabolites between rectal and sigmoid cancers.

Results

The prognosis in CRC with different sites is significantly different. The closer to the anus predicted longer survival time. The difference between genes and co-expression pairs in CRC with different sites were constructed. The relative abundance of 112 mRNAs and 26 lncRNAs correlated with the sites of CRC were listed. Nine differentially expressed genes at different sites of CRC were correlated with prognosis. A drug-gene interaction network contained 227 drug-gene pairs were built. The relative abundance of gut bacteria and gut fungus, and the content of microbe-related metabolites were statistically different between rectal and sigmoid cancers.

Conclusions

There are many differences in prognosis, genome, drug targets, gut microbiome, and microbial metabolome in different colorectal cancer sites. These findings may improve our understanding of the role of the CRC sites in personalized and precision medicine.
The clinical characteristics and molecular mechanism of pituitary adenoma associated with meningioma
Authors: Zhu Haibo , Miao Yazhou , Shen Yutao , Guo Jing , Xie Weiyan , Zhao Sida , Dong Wei , Zhang Yazhuo , Li Chuzhong
Published: October 2019

Background

Pituitary adenoma and meningioma are the most common benign tumors in the central nervous system. Pituitary adenoma associated with meningioma (PAM) is a rare disease and the clinical features and mechanisms of PAM are unclear.

Methods

We summarized the clinical data of 57 PAM patients and compared with sporadic pituitary adenoma (SPA) and sporadic meningioma (SM). 5 pituitary adenomas of PAM and 5 SPAs were performed ceRNA microarray. qRT-PCR, Western Blot, siMEN1 and rapamycin inhibition experiment were validated for ceRNA microarray.

Results

Clinical variable analyses revealed that significant correlations between PAM and female sex as well as older age when compared with SPA and significant correlations between PAM and transitional meningioma as well as older age when compared with SM. Additionally, the characteristics of PAM were significantly different for MEN1 patients. Functional experiments showed lower expression of MEN1 can upregulate mTOR signaling, in accordance with the result of ceRNA microarray. Rapamycin treatment promotes apoptosis in primary pituitary adenoma and meningioma cells of PAM.

Conclusions

MEN1 plays an important role in PAM by upregulating mTOR signaling pathway. Rapamycin represents a potential therapeutic strategy for PAM in the future.
Pharmacological and chemogenetic orexin/hypocretin intervention ameliorates Hipp-dependent memory impairment in the A53T mice model of Parkinson’s disease
Authors: Stanojlovic Milos , Pallais Jean Pierre , Lee Michael K. , Kotz Catherine M.
Published: October 2019

Parkinson’s disease (PD), classically defined as a progressive motor disorder accompanied with dopaminergic neuron loss and presence of Lewy bodies, is the second most common neurodegenerative disease. PD also has various non-classical symptoms, including cognitive impairments. In addition, inflammation and astrogliosis are recognized as an integral part of PD pathology. The hippocampus (Hipp) is a brain region involved in cognition and memory, and the neuropeptide orexin has been shown to enhance learning and memory. Previous studies show impairments in Hipp-dependent memory in a transgenic mouse model of Parkinson’s disease (A53T mice), and we hypothesized that increasing orexin tone will reverse this. To test this, we subjected 3, 5, and 7-month old A53T mice to a Barnes maze and a contextual object recognition test to determine Hipp dependent memory. Inflammation and astrogliosis markers in the Hipp were assessed by immuno-fluorescence densitometry. The data show that early cognitive impairment is coupled with an increase in expression of inflammatory and astrogliosis markers. Next, in two separate experiments, mice were given intra-hippocampal injections of orexin or chemogenetic viral injections of an orexin neuron specific Designer Receptor Exclusively Activated by Designer Drug (DREADD). For the pharmacological approach mice were intracranially treated with orexin A, whereas the chemogenetic approach utilized clozapine N-oxide (CNO). Both pharmacological orexin A intervention as well as chemogenetic activation of orexin neurons ameliorated Hipp-dependent early memory impairment observed in A53T mice. This study implicates orexin in PD-associated cognitive impairment and suggests that exogenous orexin treatment and/or manipulation of endogenous orexin levels may be a potential strategy for addressing early cognitive loss in PD.
Safety and tolerability of Meningococcus B vaccine in patients with chronical medical conditions (CMC)
Authors: Nicolosi L. , Rizzo C. , Gattinara G. Castelli , Mirante N. , Bellelli E. , Bianchini C. , Pansini V. , Villani A.
Published: October 2019

Background

Invasive meningococcal disease is a serious global health threat in the world; in 2016, the European Centre for Disease Control and Prevention reported 3280 confirmed cases (including 304 deaths) of Invasive Meningococcal Diseases in Europe. In Italy, in 2017 were reported 200 cases 41% of which due to menB serogroup. From January 2013 the European Medicines Agency (EMA) has authorized the marketing of the meningococcal B vaccine 4CMenB.

Methods

The study aimed to evaluate and complement the safety profile of 4CMenB in high risk children accessing the vaccine service of the Bambino Gesù Children’s Hospital. All individuals aged six weeks or more receiving the meningococcal 4CMenB (Bexsero®) vaccine that approached the vaccine Centre at the Bambino Gesù Children’s Hospital in Rome, were asked to participate. All parents or caregivers of vaccinated individuals in the study period, were recruited and requested to answer to a questionnaire on adverse events following immunization (AEFI) observed after 7 days, starting from the date of vaccination.

Results

During the study period (October 2016–October 2017), we collected 157 completed questionnaires (out of 200 distributed). Of those 132 were first doses and 25 were booster administered doses. The median age of the study population was 4.5 years (range 0.29 to 26.8 years), the majority of subjects were high-risk individuals (64%) with chronic health conditions. Overall, 311 adverse events were reported in the 7 days after vaccine administration. In particular 147 events (47%) after administration of first dose and 58 (19%) after the booster doses. A large majority of those events, were of little clinical importance and concentrated in the 24 h after vaccine administration. No hospitalizations or Emergency Department access were reported.

Conclusions

Results of our study demonstrated that the Bexsero® vaccine is almost well tolerated, with a low incidence of severe AEFIs. Our results also shown that the occurrence of AEFIs is similar within healthy and high risk children.
Adaptive mechanical ventilation with automated minimization of mechanical power—a pilot randomized cross-over study
Authors: Becher Tobias , Adelmeier Anna , Frerichs Inéz , Weiler Norbert , Schädler Dirk
Published: October 2019

Background

Adaptive mechanical ventilation automatically adjusts respiratory rate (RR) and tidal volume (VT) to deliver the clinically desired minute ventilation, selecting RR andVTbased on Otis’ equation on least work of breathing. However, the resultingVTmay be relatively high, especially in patients with more compliant lungs. Therefore, a new mode of adaptive ventilation (adaptive ventilation mode 2, AVM2) was developed which automatically minimizes inspiratory power with the aim of ensuring lung-protective combinations ofVTand RR. The aim of this study was to investigate whether AVM2 reducesVT, mechanical power, and driving pressure (ΔPstat) and provides similar gas exchange when compared to adaptive mechanical ventilation based on Otis’ equation.

Methods

A prospective randomized cross-over study was performed in 20 critically ill patients on controlled mechanical ventilation, including 10 patients with acute respiratory distress syndrome (ARDS). Each patient underwent 1 h of mechanical ventilation with AVM2 and 1 h of adaptive mechanical ventilation according to Otis’ equation (adaptive ventilation mode, AVM). At the end of each phase, we collected data onVT, mechanical power, ΔP, PaO2/FiO2ratio, PaCO2, pH, and hemodynamics.

Results

Comparing adaptive mechanical ventilation with AVM2 to the approach based on Otis’ equation (AVM), we found a significant reduction inVTboth in the whole study population (7.2 ± 0.9 vs. 8.2 ± 0.6 ml/kg,p <  0.0001) and in the subgroup of patients with ARDS (6.6 ± 0.8 ml/kg with AVM2 vs. 7.9 ± 0.5 ml/kg with AVM,p <  0.0001). Similar reductions were observed for ΔPstat(whole study population: 11.5 ± 1.6 cmH2O with AVM2 vs. 12.6 ± 2.5 cmH2O with AVM,p <  0.0001; patients with ARDS: 11.8 ± 1.7 cmH2O with AVM2 and 13.3 ± 2.7 cmH2O with AVM,p = 0.0044) and total mechanical power (16.8 ± 3.9 J/min with AVM2 vs. 18.6 ± 4.6 J/min with AVM,p = 0.0024; ARDS: 15.6 ± 3.2 J/min with AVM2 vs. 17.5 ± 4.1 J/min with AVM,p = 0.0023). There was a small decrease in PaO2/FiO2(270 ± 98 vs. 291 ± 102 mmHg with AVM,p = 0.03; ARDS: 194 ± 55 vs. 218 ± 61 with AVM,p = 0.008) and no differences in PaCO2, pH, and hemodynamics.

Conclusions

Adaptive mechanical ventilation with automated minimization of inspiratory power may lead to more lung-protective ventilator settings when compared with adaptive mechanical ventilation according to Otis’ equation.

Trial registration

The study was registered at the German Clinical Trials Register (DRKS00013540) on December 1, 2017, before including the first patient.
Neuropsychological management of multiple sclerosis: evaluation of a supervised and customized cognitive rehabilitation program for self-used at home (SEPIA): protocol for a randomized controlled trial
Authors: Harand Caroline , Daniel France , Mondou Audrey , Chevanne Damien , Creveuil Christian , Defer Gilles
Published: October 2019

Background

Cognitive and mood disorders negatively impact daily life in patients with multiple sclerosis (MS). Pharmacological treatments did not demonstrate any effect on cognition compared with cognitive rehabilitation (CR). However, if CR programs offer promising results on cognition, they are less consistent concerning mood and quality of life (QoL). In this context, we designed a randomized controlled trial to evaluate the efficacy of an innovative computerized CR program, conducted at home, on QoL. Secondary objectives will estimate the improvement, or the stabilization over time, of patients’ cognitive performances and their emotional affects.

Methods

Forty MS patients (relapsing-remitting or secondary progressive forms) who have cognitive impairment will be recruited for the trial (called SEPIA-NCT03471338) and randomly assigned to either the experimental group or the control group. Patients randomly assigned in the experimental group will perform a home-based CR program with psychological support during eight consecutive weeks. CR will be based on computerized cognitive exercises from the PRESCO® software developed by HAPPYneuron©. Training sessions (three sessions of 45 min per week) will consist of short exercises evaluating a broad range of cognitive domains and will be personalized for each patient (tracking tool and supervised guidance). The control group, designed to control for non-specific elements of the intervention, will receive only psychological support consisting of various issues related to MS, such as everyday cognitive-related difficulties or management of emotions. QoL, assessed by the MUSIQOL (Multiple Sclerosis International Quality Of Life) questionnaire, will be evaluated three times (at baseline and after 1 week and 25 weeks after home-based intervention) as well as secondary outcomes measuring self-esteem, cognition, depression, anxiety, metacognition, fatigue, and sleep quality. Given the expected MUSIQOL variation, the inclusion of 20 patients per group (alpha risk 5% and power 80%) will be required.

Discussion

Evidence suggests that computerized programs may be a practice option for CR for people with MS, but there is a paucity of studies evaluating QoL. We hope that this innovative program will highlight such benefits over time in patients’ daily life. In the future, such programs will allow a wider range of available therapeutic options for MS patients with cognitive impairment and for practitioners in charge of their care.

Trial registration

ClinicalTrials.gov identifier: NCT03471338. Retrospectively registered on 25 April 2018. https://clinicaltrials.gov/ct2/show/NCT03471338?term=NCT03471338&cond=Multiple+Sclerosis&draw=2&rank=1.
Reliability of crowdsourcing as a method for collecting emotions labels on pictures
Authors: Korovina Olga , Baez Marcos , Casati Fabio
Published: October 2019

Objective

In this paper we study if and under what conditions crowdsourcing can be used as a reliable method for collecting high-quality emotion labels on pictures. To this end, we run a set of crowdsourcing experiments on the widely used IAPS dataset, using the Self-Assessment Manikin (SAM) emotion collection instrument, in order to rate pictures on valence, arousal and dominance, and explore the consistency of crowdsourced results across multiple runs (reliability) and the level of agreement with the gold labels (quality). In doing so, we explored the impact of targeting populations of different level of reputation (and cost) and collecting varying numbers of ratings per picture.

Results

The results tell us that crowdsourcing can be a reliable method, reaching excellent levels of reliability and agreement with only 3 ratings per picture for valence and 8 per arousal, with only marginal difference between target populations. Results for dominance were very poor, echoing previous studies on the data collection instrument used. We also observed that specific types of content generate diverging opinions in participants (leading to higher variability or multimodal distributions), which remain consistent across pictures of the same theme. These can inform the data collection and exploitation of crowdsourced emotion datasets.
Costing for universal health coverage: insight into essential economic data from three provinces in Cambodia
Authors: Jacobs Bart , Hui Kelvin , Lo Veasnakiry , Thiede Michael , Appelt Bernd , Flessa Steffen
Published: October 2019

Background

Knowledge of the costs of health services improves health facility management and aids in health financing for universal health coverage. Because of resource requirements that are often not present in low- and middle-income countries, costing exercises are rare and infrequent. Here we report findings from the initial phase of establishing a routine costing system for health services implemented in three provinces in Cambodia.

Methods

Data was collected for the 2016 financial year from 20 health centres (including four with beds) and five hospitals (three district hospitals and two provincial hospitals). The costs to the providers for health centres were calculated using step-down allocations for selected costing units, including preventive and curative services, delivery, and patient contact, while for hospitals this was complemented with bed-day and inpatient day per department. Costs were compared by type of facility and between provinces.

Results

All required information was not readily available at health facilities and had to be recovered from various sources. Costs per outpatient consultation at health centres varied between provinces (from US$2.33 to US$4.89), as well as within provinces. Generally, costs were inversely correlated with the quantity of service output. Costs per contact were higher at health centres with beds than health centres without beds (US$4.59, compared to US$3.00). Conversely, costs for delivery were lower in health centres with beds (US$128.7, compared to US$413.7), mainly because of low performing health centres without beds. Costs per inpatient-day varied from US$27.61 to US$55.87 and were most expensive at the lowest level hospital.

Conclusions

Establishing a routine health service costing system appears feasible if recording and accounting procedures are improved. Information on service costs by health facility level can provide useful information to optimise the use of available financial and human resources.
Attribute development and level selection for a discrete choice experiment to elicit the preferences of health care providers for capitation payment mechanism in Kenya
Authors: Obadha Melvin , Barasa Edwine , Kazungu Jacob , Abiiro Gilbert Abotisem , Chuma Jane
Published: October 2019

Background

Stated preference elicitation methods such as discrete choice experiments (DCEs) are now widely used in the health domain. However, the “quality” of health-related DCEs has come under criticism due to the lack of rigour in conducting and reporting some aspects of the design process such as attribute and level development. Superficially selecting attributes and levels and vaguely reporting the process might result in misspecification of attributes which may, in turn, bias the study and misinform policy. To address these concerns, we meticulously conducted and report our systematic attribute development and level selection process for a DCE to elicit the preferences of health care providers for the attributes of a capitation payment mechanism in Kenya.

Methodology

We used a four-stage process proposed by Helter and Boehler to conduct and report the attribute development and level selection process. The process entailed raw data collection, data reduction, removing inappropriate attributes, and wording of attributes. Raw data was collected through a literature review and a qualitative study. Data was reduced to a long list of attributes which were then screened for appropriateness by a panel of experts. The resulting attributes and levels were worded and pretested in a pilot study. Revisions were made and a final list of attributes and levels decided.

Results

The literature review unearthed seven attributes of provider payment mechanisms while the qualitative study uncovered 10 capitation attributes. Then, inappropriate attributes were removed using criteria such as salience, correlation, plausibility, and capability of being traded. The resulting five attributes were worded appropriately and pretested in a pilot study with 31 respondents. The pilot study results were used to make revisions. Finally, four attributes were established for the DCE, namely, payment schedule, timeliness of payments, capitation rate per individual per year, and services to be paid by the capitation rate.

Conclusion

By rigorously conducting and reporting the process of attribute development and level selection of our DCE,we improved transparency and helped researchers judge the quality.
Online non-negative discriminative dictionary learning for tracking
Authors: Wang Weisong , Yang Fei , Zhang Hongzhi
Published: October 2019

In this paper, online non-negative discriminative dictionary learning for tracking is proposed, which combines the advantages of the global dictionary learning model and the class-specific dictionary learning model. The previous algorithm based on general dictionary learning does not take into account the inter-class relations between classes and make full use of tag information. In order to improve the classification ability of dictionaries, the class correlation was proposed to guide the learning of discriminant dictionaries, which makes full use of the correlation and difference between the atomic classes of dictionaries and introduces the tag information of the categories to improve the discriminant ability of dictionaries. For this purpose, the Huber loss function and the Fisher weight coefficient is used in the discriminative term to improve computational efficiency. In addition, non-negative constraints is added on dictionaries to enhance the performance. The OTB50 and OTB100 datasets are used to evaluate our tracker and compare with related algorithm. The experimental results show that our method performs much better than the tracking method compared in this paper.
On a weak solution matching up with the double degenerate parabolic equation
Authors: Weng Sujun
Published: October 2019

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Hearing and justice: The link between hearing impairment in early childhood and youth offending in Aboriginal children living in remote communities of the Northern Territory, Australia
Authors: He Vincent Yaofeng , Su Jiunn-Yih , Guthridge Steven , Malvaso Catia , Howard Damien , Williams Tamika , Leach Amanda
Published: October 2019

Background

High prevalence of chronic middle ear disease has persisted in Australian Aboriginal children, and the related hearing impairment (HI) has been implicated in a range of social outcomes. This study investigated the association between HI in early childhood and youth offending.

Method

This was a retrospective cohort study of 1533 Aboriginal children (born between 1996 and 2001) living in remote Northern Territory communities. The study used linked individual-level information from health, education, child protection and youth justice services. The outcome variable was a youth being “found guilty of an offence”. The key explanatory variable, hearing impairment, was based on audiometric assessment. Other variables were: child maltreatment notifications, Year 7 school enrolment by mother, Year 7 school attendance and community ‘fixed- effects’. The Cox proportional hazards model was used to estimate the association between HI and youth offending; and the Royston R2 measure to estimate the separate contributions of risk factors to youth offending.

Results

The proportion of hearing loss was high in children with records of offence (boys: 55.6%, girls: 36.7%) and those without (boys: 46.1%; girls: 49.0%). In univariate analysis, a higher risk of offending was found among boys with moderate or worse HI (HR: 1.77 [95% CI: 1.05–2.98]) and mild HI (HR: 1.54 [95% CI:1.06–2.23]). This association was attenuated in multivariable analysis (moderate HI, HR: 1.43 [95% CI:0.78–2.62]; mild HI, HR: 1.37 [95% CI: 0.83–2.26]). No evidence for an association was found in girls. HI contributed 3.2% and 6.5% of variation in offending among boys and girls respectively. Factors contributing greater variance included: community ‘fixed-effects’ (boys: 14.6%, girls: 36.5%), child maltreatment notification (boys: 14.2%, girls: 23.9%) and year 7 school attendance (boys: 7.9%; girls 12.1%). Enrolment by mother explained substantial variation for girls (25.4%) but not boys (0.2%).

Conclusion

There was evidence, in univariate analysis, for an association between HI and youth offending for boys however this association was not evident after controlling for other factors. Our findings highlight a range of risk factors that underpin the pathway to youth-offending, demonstrating the urgent need for interagency collaboration to meet the complex needs of vulnerable children in the Northern Territory.
Risk factors of frailty and death or only frailty after intensive care in non-frail elderly patients: a prospective non-interventional study
Authors: Launey Yoann , Jacquet Hervé , Arnouat Matthieu , Rousseau Chloe , Nesseler Nicolas , Seguin Philippe
Published: October 2019

Background

Frailty status is recognized as an important parameter in critically ill elderly patients, but nothing is known about outcomes in non-frail patients regarding the development of frailty or frailty and death after intensive care. The aim of this study was to determine risk factors for frailty and death or only frailty 6 months after intensive care unit (ICU) admission in non-frail patients ≥ 65 years.

Methods

A prospective non-interventional study performed in an academic ICU from February 2015 to February 2016 included non-frail ≥ 65-year-old patients hospitalized for > 24 h in the ICU. Frailty was assessed by calculating the frailty index (FI) at admission and 6 months later. Patients who remained non-frail (FI < 0.2) were compared to patients who presented frailty (FI ≥ 0.2) and those who presented frailty and death at 6 months.

Results

Among 974 admissions, 136 patients were eligible for the study and 88 patients were analysed at 6 months (non-frail n = 34, frail n = 29, death n = 25). Multivariable analysis showed that mechanical ventilation duration was an independent risk factor for frailty/death at 6 months (per day of mechanical ventilation, odds ratio [OR] = 1.11; 95% confidence interval [CI] 1.04–1.19, p = 0.002). When excluding patients who died, mechanical ventilation duration remained the sole risk factor for frailty at 6 months (OR = 1.19; 95% CI 1.07–1.33, p = 0.001).

Conclusion

Mechanical ventilation duration was the sole predictive factor of frailty and death or only frailty 6 months after ICU hospitalization in initially non-frail patients.
Effects of denosumab on bone mineral density and bone turnover markers in rheumatoid arthritis patients switching from bisphosphonates
Authors: Kaneko Tetsuya , Okamura Koichi , Yonemoto Yukio , Okura Chisa , Suto Takahito , Tachibana Masahiro , Sakane Hideo , Inoue Makoto , Chikuda Hirotaka
Published: October 2019

Background

To compare the efficacy of 12-month denosumab treatment on bone mineral density (BMD) and bone turnover markers (BTMs) between treatment-naïve osteoporosis patients with rheumatoid arthritis (RA) and those with previous bisphosphonate (BP) therapy.

Methods

A total of 36 RA patients with osteoporosis completed 12-month follow-up. Twenty-five patients were osteoporotic treatment-naïve (naïve group), and 11 patients were previously treated with BPs (switch group) (average 7.9 years). BMD and BTMs were measured before and 6 and 12 months after treatment.

Results

BTM levels were higher in the naïve group at baseline. However, the same level of suppression was achieved at 6 months in both groups. Spine BMD increased significantly in both groups. There was no significant difference in the mean percent changes of BMD of the spine (naïve group: 6.8 ± 0.8, switch group: 5.1 ± 1.5), femoral neck (2.9 ± 1.4, 2.9 ± 1.3), and total hip (1.7 ± 0.9, 1.4 ± 1.1) between these two groups at 12 months.

Conclusions

The effects of denosumab on BMD and BTMs of the switch group after long-term BP treatment are comparable to those of the naïve group in RA patients. Thus, switching BPs to denosumab is one of the useful options to treat osteoporosis with RA.
The peripheral blood transcriptome in septic cardiomyopathy: an observational, pilot study
Authors: Cirulis Meghan M. , Beesley Sarah J. , Wilson Emily L. , Stubben Chris , Olsen Troy D. , Hirshberg Eliotte L. , Smith Lane M. , Lanspa Michael J. , Abraham Theodore P. , Grissom Colin K. , Rondina Matthew T. , Brown Samuel M.
Published: October 2019

Background

Septic cardiomyopathy (SCM) is common in sepsis and associated with increased morbidity and mortality. Left ventricular global longitudinal strain (LV GLS), measured by speckle tracking echocardiography, allows improved identification of impaired cardiac contractility. The peripheral blood transcriptome may be an important window into SCM pathophysiology. We therefore studied the peripheral blood transcriptome and LV GLS in a prospective cohort of patients with sepsis.

Results

In this single-center observational pilot study, we enrolled adult patients (age > 18) with sepsis within 48 h of admission to the ICU. SCM was defined as LV GLS > − 17% based on echocardiograms performed within 72 h of admission. We enrolled 27 patients, 24 of whom had high-quality RNA results; 18 (75%) of 24 had SCM. The group was 50% female and had a median (IQR) age of 59.5 (48.5–67.0) years and admission APACHE II score of 21.0 (16.0–32.3). Forty-six percent had septic shock. After filtering for low-expression and non-coding genes, 15,418 protein coding genes were expressed and 73 had significantly different expression between patients with vs. without SCM. In patients with SCM, 43 genes were upregulated and 30 were downregulated. Pathway analysis identified enrichment in type 1 interferon signaling (adjusted p < 10−5).

Conclusions

In this hypothesis-generating study, SCM was associated with upregulation of genes in the type 1 interferon signaling pathway. Interferons are cytokines that stimulate the innate and adaptive immune response and are implicated in the early proinflammatory and delayed immunosuppression phases of sepsis. While type 1 interferons have not been implicated previously in SCM, interferon therapy (for viral hepatitis and Kaposi sarcoma) has been associated with reversible cardiomyopathy, perhaps suggesting a role for interferon signaling in SCM.
Evaluation of FGF10 as a candidate gene for high myopia in a Han Chinese population
Authors: Jiang Lingxi , Luo Dongyan , Wang Tingting , Zheng Rui , Zhai Yaru , Liu Xiaoqi , Gong Bo , Wu Zhengzheng , Yang Yin , Yang Zhenglin , Shi Yi
Published: October 2019

Background

Fibroblast growth factor 10 (FGF10) is implicated in the growth and development of the eye. Four singles nucleotide polymorphisms (SNPs) in the FGF10 gene (including rs1384449, rs339501, rs12517396 and rs10462070) were found to be associated with extreme myopia (EM, refractive error ≤ − 10.0 diopters) in Japanese and Chinese Taiwan population. This case-control association study was conducted to explore the relationship between these four SNPs and high myopia in a western Chinese population.

Methods

A total of 869 high myopia patients (HM, including 485 EM patients) and 899 healthy controls were recruited. These four SNPs were genotyped using the ABI SNaPshot method. Five genetic models (allelic, homozygous, heterozygous, dominant, and recessive) were applied to further evaluate the possible correlation between the SNPs and high myopia. The linkage-disequilibrium block (LD) structure was tested by Haploview Software.

Results

In our study, no statistically significant differences were found between HM/EM patients and controls after Bonferroni multiple-correction (P > 0.05) in the allele frequencies of these four SNPs in the FGF10 gene. We further found that rs12517396AA and rs10462070GG carriers showed a decreased risk of HM/EM compared with rs12517396AC + CC and rs10462070GA + AA carriers (P = 0.045, OR = 0.366; P = 0.021, OR = 0.131; P = 0.03, OR = 0.341; P = 0.015, OR = 0.122; respectively). Additionally, rs12517396AA and rs10462070GG carriers showed the same decreased risk of HM/EM compared with rs12517396CC and rs10462070AA carriers (P = 0.048, OR = 0.370; P = 0.023, OR = 0.133; P = 0.032, OR = 0.346; P = 0.017, OR = 0.126). However, these significant associations between rs12517396/rs10462070 and HM/EM disappeared after Bonferroni multiple-correction (P > 0.05).

Conclusion

Our findings indicate that rs12517396 and rs10462070 had marginal association with HM and EM. The other two common polymorphisms in FGF10 unlikely have significant effects in the genetic predisposition to HM/EM in western Chinese population. Further replication studies are needed to validate our findings in both animal models and human genetic epidemiologic studies.
Investigation of factors that cause insulin precipitation and/or amyloid formation in insulin formulations
Authors: Ohno Yui , Seki Tomohiro , Kojima Yu , Miki Ryotaro , Egawa Yuya , Hosoya Osamu , Kasono Keizo , Seki Toshinobu
Published: October 2019

Background

Multiple daily subcutaneous injections (MDSIs) are mainly used for formulating an insulin therapy for diabetic patients; however, they also cause insulin-derived amyloidosis (IDA) and lead to poor glycemic control. In addition, for the continuous subcutaneous insulin infusion system (CSII), precipitation frequently causes catheter occlusion and, if the precipitate in the formulations is amyloid, the injection of the insoluble amyloid into the subcutaneous tissue leads to IDA. The aim of this study was to conduct in vitro experiments and present a situation where insulin formulations cause precipitation and amyloid formation.

Methods

Humulin®R and NovoRapid® were used as model formulations for MDSIs and CSII, respectively. The generation of the precipitation was evaluated by measuring turbidity, and amyloid formation was evaluated by using Thioflavin T. Humulin®R was mixed with saline buffer solutions and glucose solutions to evaluate the effect of dilution. In addition, we created an experimental system to consider the effect of the time course of condition changes, and investigated the effects of insulin concentration, m-cresol existence, and pH change on the generation of the precipitate and amyloid in the formulation.

Results

In both the original and diluted formulations, physical stimulation resulted in the formation of a precipitate, which in most cases was an amyloid. The amyloid was likely to be formed at a near neutral pH. On the contrary, although a precipitate formed when the pH was decreased to near the isoelectric point, this precipitate was not an amyloid. Further decreases in pH resulted in the formation of amyloids, suggesting that both the positive and negative charged states of insulin tended to form amyloids. The formulation additive m-cresol suppressed amyloid formation. When additives were removed from the formulation, the amyloid-containing gel was formed in the field of substance exchange.

Conclusions

To consider changes in conditions that may occur for insulin formulations, the relationship between the formation of precipitates and amyloids was demonstrated in vitro by using insulin formulations. From the in vitro study, m-cresol was shown to have an inhibitory effect on amyloid formation.
Perforation of small intestinal metastasis of lung adenocarcinoma treated with pembrolizumab: a case report
Authors: Sato Shoki , Senmaru Naoto , Ishido Keita , Saito Takahiro , Poudel Saseem , Muto Jun , Syouji Yasuhito , Hase Ryunosuke , Hirano Satoshi
Published: October 2019

Background

Pembrolizumab is an immune checkpoint inhibitor and is an anti-human programmed cell death-1 (PD-1) monoclonal antibody. Pembrolizumab is used for non-small cell lung carcinoma with high programmed cell death ligand-1 (PD-L1) expression. It has been found that better overall survival can be obtained using pembrolizumab compared to the existing chemotherapy. We report a case of perforation of small intestinal metastasis after pembrolizumab treatment.

Case presentation

A 62-year-old man was treated by pembrolizumab for PD-L1 highly expressed lung adenocarcinoma, with multiple metastasis (small intestinal, lymph nodes, and bone). The treatment was stopped owing to drug-induced pneumonitis. One month after drug withdrawal, the patient visited the emergency department of our hospital with the complaint of severe stomachache. He had a rigid abdomen and generalized tenderness, and computed tomography scans showed free air within the abdomen. We diagnosed bowel perforation and performed emergency surgery. Surgical findings revealed multiple small intestine metastasis and mesenteric lymph node metastasis. Perforation was found in the metastatic site in the jejunum located around 40 cm anal to Treitz’s ligament. This perforated part was resected, and functional end-to-end anastomosis was performed using linear staplers. The post-operative course was uneventful. Pathological examination revealed lung adenocarcinoma metastasis at the perforation site, and the effectiveness of pembrolizumab was grade 1b (Japanese Classification of the Colorectal Carcinoma, seventh edition).

Conclusions

This is the first report of perforation of small intestinal metastasis of lung adenocarcinoma after pembrolizumab treatment. Because pembrolizumab causes some side effects, particularly autoimmune side effects, careful attention during treatment is warranted.