bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of a 4-lncRNA signature predicting prognosis of patients with non-small cell lung cancer: a multicenter study in China
Authors: Wang Rui-Qi , Long Xiao-Ran , Ge Chun-Lei , Zhang Mei-Yin , Huang Long , Zhou Ning-Ning , Hu Yi , Li Rui-Lei , Li Zhen , Chen Dong-Ni , Zhang Lan-Jun , Wen Zhe-Sheng , Mai Shi-Juan , Wang Hui-Yun
Published: August 2020

Background

Previous findings have indicated that the tumor, nodes, and metastases (TNM) staging system is not sufficient to accurately predict survival outcomes in patients with non-small lung carcinoma (NSCLC). Thus, this study aims to identify a long non-coding RNA (lncRNA) signature for predicting survival in patients with NSCLC and to provide additional prognostic information to TNM staging system.

Methods

Patients with NSCLC were recruited from a hospital and divided into a discovery cohort (n = 194) and validation cohort (n = 172), and detected using a custom lncRNA microarray. Another 73 NSCLC cases obtained from a different hospital (an independent validation cohort) were examined with qRT-PCR. Differentially expressed lncRNAs were determined with the Significance Analysis of Microarrays program, from which lncRNAs associated with survival were identified using Cox regression in the discovery cohort. These prognostic lncRNAs were employed to construct a prognostic signature with a risk-score method. Then, the utility of the prognostic signature was confirmed using the validation cohort and the independent cohort.

Results

In the discovery cohort, we identified 305 lncRNAs that were differentially expressed between the NSCLC tissues and matched, adjacent normal lung tissues, of which 15 are associated with survival; a 4-lncRNA prognostic signature was identified from the 15 survival lncRNAs, which was significantly correlated with survivals of NSCLC patients. This signature was further validated in the validation cohort and independent validation cohort. Moreover, multivariate Cox analysis demonstrates that the 4-lncRNA signature is an independent survival predictor. Then we established a new risk-score model by combining 4-lncRNA signature and TNM staging stage. The receiver operating characteristics (ROC) curve indicates that the prognostic value of the combined model is significantly higher than that of the TNM stage alone, in all the cohorts.

Conclusions

In this study, we identified a 4-lncRNA signature that may be a powerful prognosis biomarker and can provide additional survival information to the TNM staging system.
A case report of a novel compound heterozygous mutation in a Brazilian patient with deficiency of Interleukin-1 receptor antagonist (DIRA)
Authors: Mendonça Leonardo Oliveira , Grossi Alice , Caroli Francesco , de Oliveira Robson Aguiar , Kalil Jorge , Castro Fabio Fernandes Morato , Pontillo Alessandra , Ceccherini Isabella , Barros Myrthes Anna Maragna Toledo , Gattorno Marco
Published: August 2020

Background

Deficiency of the natural antagonist of interleukin-1 was first described in 2009 and so far 20 patients has been reported. In Brazil just two cases have been reported both carrying the same homozygous 15 bp deletion. Blocking interleukin-1 has changed rate survival for DIRA patients. The use of anakinra and rilonacept has been reported safe and efficient, whereas the selective blockade of interleukin-1 beta, using the monoclonal antibody canakinumab has been reported in a single case only.

Case presentation

Here we report a case of a 7 years old Brazilian boy that presented with recurrent episodes of systemic inflammation with severe disabling osteomyelitis with mild pustular skin rash. A Next Generation Sequencing gene panel allowed to detect two pathogenic mutations in the IL1RN gene, described in compound heterozygosity. Corticosteroids was effective in controlling inflammation and anti-IL1 beta blocker triggered disease flare. Complete clinical control could be achieved using IL-1 receptor antagonist.

Conclusions

DIRA is a severe, life threatening autoinflammatory condition with low numbers of patients described all over the world. The mutation p.Asp72_Ile76del in IL1RN is presented in all Brazilian DIRA patients already described and p.Q45* (rs1019766125) is a new mutation affecting the IL1RN gene. Following the pathogenesis of DIRA, blocking both subunits of interleukin one as well as antagonizing the receptor using anakinra or rilonacept seems to be effective. There is just one report using canakinumab for the treatment of DIRA and this is the first report of disease flare using this drug.
MicroRNA-195 prevents hippocampal microglial/macrophage polarization towards the M1 phenotype induced by chronic brain hypoperfusion through regulating CX3CL1/CX3CR1 signaling
Authors: Mao Meng , Xu Yi , Zhang Xin-Yu , Yang Lin , An Xiao-bin , Qu Yang , Chai Ya-ni , Wang Yan-Ru , Li Ting-ting , Ai Jing
Published: August 2020

Background

Microglial polarization is a dynamic response to acute brain hypoxia induced by stroke and traumatic brain injury (TBI). However, studies on the polarization of microglia in chronic cerebral circulation insufficiency (CCCI) are limited. Our objective was to investigate the effect of CCCI on microglial polarization after chronic brain hypoperfusion (CBH) and explore the underlying molecular mechanisms.

Methods

CBH model was established by bilateral common carotid artery occlusion (2-vessel occlusion, 2VO) in rats. Using the stereotaxic injection technique, lenti-pre-miR-195and anti-miR-195oligonucleotide fragments (lenti-pre-AMO-miR-195) were injeted into the CA1 region of the hippocampus to construct animal models with high or low expression ofmiR-195. Immunofluorescence staining and flow cytometry were conducted to examine the status of microglial polarization. In vitro, Transwell co-culture system was taken to investigate the role ofmiR-195on neuronal-microglial communication through CX3CL1-CX3CR1 signaling. Quantitative real-time PCR was used to detect the level ofmiR-195and inflammatory factors. The protein levels of CX3CL1 and CX3CR1 were evaluated by both western blot and immunofluorescence staining.

Results

CBH induced by 2VO initiated microglial/macrophage activation in the rat hippocampus from 1 week to 8 weeks, as evaluated by increased ratio of (CD68+and CD206+)/Iba-1 immunofluorescence. And the microglial/macrophage polarization was shifted towards the M1 phenotype at 8 weeks following CBH. The expression of CX3CL1 and CX3CR1 was increased in the hippocampus of 2VO rats at 8 weeks. An in vitro study in a Transwell co-culture system demonstrated that transfection of either primary-cultured neonatal rat neurons (NRNs) or microglial BV2 cells with AMO-195-induced M1 polarization of BV2 cells and increased CX3CL1 and CX3CR1 expression and that these effects were reversed bymiR-195mimics. Furthermore, the upregulation ofmiR-195induced by lenti-pre-miR-195injection prevented microglial/macrophage polarization to M1 phenotype triggered by hippocampal injection of lenti-pre-AMO-miR-195and 2VO surgery.

Conclusions

Our findings conclude that downregulation ofmiR-195in the hippocampus is involved in CBH-induced microglial/macrophage polarization towards M1 phenotype by governing communication between neurons and microglia through the regulation of CX3CL1 and CX3CR1 signaling. This indicates thatmiR-195may provide a new strategy for clinical prevention and treatment of CBH.
Primary and secondary three-month outcomes of a cluster-randomized trial of home-based postpartum contraceptive delivery in southwest Trifinio, Guatemala
Authors: Harrison Margo S. , Bunge-Montes Saskia , Rivera Claudia , Jimenez-Zambrano Andrea , Heinrichs Gretchen , Bolanos Antonio , Asturias Edwin , Berman Stephen , Sheeder Jeanelle
Published: August 2020

Design

This a cluster-randomized parallel arm pragmatic trial to observe the association of home-based postpartum contraceptive provision, including the contraceptive implant, with implant utilization rates at 3 months post-enrollment.

Methods

In a region of rural Guatemala referred to as the Southwest Trifinio, twelve communities are served by a community-based antenatal and postnatal care program. The communities were combined into eight clusters based on 2017 birth rates and randomized to receive the home-based contraceptive delivery (condoms, pills, injection, implant) during the routine 40-day postpartum visit. All participants receive comprehensive contraceptive counseling beginning at the first antenatal visit, so control clusters received this as part of routine care; this education preceded the study intervention.

Results

Once the 12 communities were combined into 8 clusters by expected birth volume and nurse team, which we expected to translate to eventual postpartum visits, the allocation sequence was generated in SAS. Of 208 women enrolled in the study, 108 were in four intervention and 100 in four control clusters. We used descriptive statistics to produce counts and percentages of characteristics of the study population overall and by intervention arm followed by univariate modeling using a mixed effects regression adjusted for cluster. Three-month contraceptive initiation rates were 56.0% in the control clusters compared to 76.8% in the intervention clusters, p < 0.001. Women in control clusters overwhelmingly opted for the injectable contraceptive (94.6%) while women in intervention clusters chose both the injection (61.5%) and the implant (33.7%), p < 0.001. Implant use by 3 months, the primary outcome of the study, was significantly higher in the intervention arm (25.9%) compared to the control arm (3.6%), p < 0.001, RR 1.3 CI [1.2, 1.4].

Conclusion

Our study was designed to respond to previously identified barriers to contraceptive uptake, and it was successful. Not only did it increase overall use of contraception by 3 months, but it shifted that contraceptive use away from short-acting methods in favor of longer-acting methods, with high continuation and satisfaction rates and no adverse outcomes reported.

Trial registration

clinicaltrials.gov, NCT04005391; Retrospectively Registered 7/2/2019,
The prevalence of psychosocial related terminology in chiropractic program courses, chiropractic accreditation standards, and chiropractic examining board testing content in the United States
Authors: Gliedt Jordan A. , Battaglia Patrick J. , Holmes Benjamin D.
Published: August 2020

Background

Spine related disorders entail biological (somatic), psychological, and social factors. Though biological factors are often emphasized, psychosocial considerations may not be receiving proper attention in the chiropractic field. Chiropractors treat spine complaints and therefore should be trained in the full spectrum of the biopsychosocial model. This study examines the use of psychosocial related terminology in United States doctor of chiropractic program (DCP) curricula, the Council on Chiropractic Education (CCE) standards, and the National Board of Chiropractic Examiners (NBCE) test plans.

Methods

Nineteen academic course catalogs, CCE curricular standards and meta-competencies, and NBCE test plans were studied. Terms containing “psycho”, “soci”, “mental”, “econom”, “cultur”, “emotion”, “determinant”, “public”, “communit”, “neighbor”, “behav”, or “cognitive” were identified in each document. Frequency of use, context of use, thematic categorization, and percentage of use compared to overall content were calculated and described.

Results

‘Public’ is the most commonly used psychosocial related term in DCP curricula. ‘Determinant’ was used in 1 DCP curriculum. The number of courses with psychosocial related terminology in course titles and course descriptions ranged from 1 to 5 and 3 to 12, respectively. Most terms are found in clinical skills, special populations, and other miscellaneous courses, with fewer terms found in psychology and public health courses. Terminology use in course titles and descriptions compared to overall content ranges from 3.40 to 14.86%. CCE uses terminology 17 times across 5 (out of 8) total meta-competencies. NBCE includes terminology in test plans I and II, but not III or IV.

Conclusions

Despite evidence suggesting the influential role of psychosocial factors in determinants of health and healthcare delivery, these factors are poorly reflected in United States DCP curricula. This underappreciation is further evidenced by the lack of representation of psychosocial terminology in NBCE parts III and IV test plans. The reasons for this are theoretical; lack of clarity or enforcement of CCE meta-competencies may contribute.
Myocardial deformation after radiotherapy: a layer-specific and territorial longitudinal strain analysis in a cohort of left-sided breast cancer patients (BACCARAT study)
Authors: Walker Valentin , Lairez Olivier , Fondard Olivier , Jimenez Gaëlle , Camilleri Jérémy , Panh Loïc , Broggio David , Bernier Marie-Odile , Laurier Dominique , Ferrières Jean , Jacob Sophie
Published: August 2020

Background

Radiotherapy for breast cancer (BC) and its resulting cardiac exposure are associated with subclinical left ventricular dysfunction characterized by early decrease of global longitudinal strain (LS) measurement based on 2D speckle-tracking echocardiography. Recent software allows multi-layer and segmental analysis of strain, which may be of interest to quantify and locate the impact of cardiac exposure on myocardial function and potentially increase the early detection of radiation-induced cardiotoxicity. The aim of the study was to evaluate whether decrease in LS 6 months after radiotherapy is layer-specific and if it varies according to the left ventricular regional level and the coronary arterial territories.

Methods

LS was measured at baseline before radiotherapy and 6 months post-radiotherapy. The LS was obtained for each myocardial layer (endocardial, mid-myocardial, epicardial), left ventricular regional level (basal, mid, apical) and coronary artery territory (left anterior descending artery (LAD), circumflex artery, right coronary artery).

Results

The study included 64 left-sided BC patients. Mean age was 58 years, mean doses to the heart, the left ventricle and the LAD were respectively 3.0, 6.7 and 16.4 Gy. The absolute decrease of LS was significant for the three layers (endocardial: − 20.0 ± 3.2% to − 18.8 ± 3.8%; mid-myocardial: − 16.0 ± 2.7% to − 15.0 ± 3.1%; epicardial: − 12.3 ± 2.5% to − 11.4 ± 2.8%, allp = 0.02), but only the relative decrease of LS in the endocardial layer was close to be significant (− 4.7%,p = 0.05). More precisely, the LS of the endocardial layer was significantly decreased for the most exposed parts of the left ventricle corresponding to the apical level (− 26.3 ± 6.0% vs. -24.2 ± 7.1%,p = 0.03) and LAD territory (− 22.8 ± 4.0% vs. -21.4 ± 4.8%,p = 0.03).

Conclusion

Six months post-radiotherapy, LS decreased predominantly in the endocardial layer of the most exposed part of the left ventricle. For precise evaluation of radiotherapy-induced cardiotoxicity and early left ventricular dysfunction, the endocardial layer-based LS might be the most sensitive parameter.

Trial registration

ClinicalTrials.gov:NCT02605512, Registered 6 November 2015 - Retrospectively registered.
Effect of facet-joint degeneration on the in vivo motion of the lower lumbar spine
Authors: Yin Jun , Liu Zhang , Li Chao , Luo Shiwei , Lai Qi , Wang Shaobai , Zhang Bin , Wan Zongmiao
Published: August 2020

Objective

This research studied the in vivo motion characteristics of the L3–S1 lumbar spine with facet-joint degeneration during functional activities.

Methods

Thirteen male and 21 female patients with facet-joint degeneration at the L3–S1 spinal region were included in the study. The L3–S1 lumbar segments of all the patients were divided into 3 groups according to the degree of facet-joints degeneration (mild, moderate, or severe). The ranges of motion (ROM) of the vertebrae were analyzed using a combination of computed tomography and dual fluoroscopic imaging techniques. During functional postures, the ROMs were compared between the 3 groups at each spinal level (L3–L4, L4–L5, and L5–S1).

Results

At L3–L4 level, the primary rotations between the mild and moderate groups during left-right twisting activity were significantly different. At L4–L5 level, the primary rotation of the moderate group was significantly higher than the other groups during flexion-extension. During left-right bending activities, a significant difference was observed only between the moderate and severe groups. At L5–S1 level, the rotation of the moderate group was significantly higher than the mild group during left-right bending activity.

Conclusions

Degeneration of the facet joint alters the ROMs of the lumbar spine. As the degree of facet-joint degeneration increased, the ROMs of the lumbar vertebra that had initially increased declined. However, when there was severe facet-joint degeneration, the ROMs of the lumbar spine declined to levels comparative to the moderate group. The relationship between the stability of the lumbar vertebra and the degree of facet-joint degeneration requires further study.
A novel prognostic model for adult patients with Hemophagocytic Lymphohistiocytosis
Authors: Zhou Jun , Zhou Jing , Wu Zhi-Qi , Goyal Hemant , Xu Hua-Guo
Published: August 2020

Background

Hemophagocytic Lymphohistiocytosis (HLH) is a type of rare disease with low survival rate. We aimed to develop a model to evaluate the six-month prognosis in adult HLH patients. The data at discharge (will be called as post-treatment) for newly diagnosed adult HLH patients was collected and independent prognostic variables were selected for inclusion in the model.

Results

Three laboratory markers were confirmed to be the independent risk factors (ferritin: hazard ratio (HR) 0.101, 95% confidence interval (CI) 0.036–0.282, P<0.001; platelets: HR 4.799, 95% CI 1.884–12.223, P = 0.001; alanine aminotransferase (ALT): HR 0.423, 95% CI 0.180–0.997, P = 0.049). These were included in the final clinical prediction model. Receiver operating characteristic (ROC) curves disclosed that this model had a better discrimination (area under the curve (AUC) = 0.842, 95% CI 0.773–0.910, P < 0.001) than each of them alone and the calibration curves aligned completely with the model predictions and actual observations. Kaplan-Meier curves revealed a significant difference in the overall survival (OS) in patients stratified by the model with higher values associated with a better OS.

Conclusion

These results point out that serum ferritin, platelets and ALT levels are independent elements of OS in adult patients with HLH, and that the proposed model have a better prognostic value than any of these markers alone.
Association between mean arterial pressure during the first 24 hours and hospital mortality in patients with cardiogenic shock
Authors: Burstein Barry , Tabi Meir , Barsness Gregory W. , Bell Malcolm R. , Kashani Kianoush , Jentzer Jacob C.
Published: August 2020

Background

The optimal MAP target for patients with cardiogenic shock (CS) remains unknown. We sought to determine the relationship between mean arterial pressure (MAP) and mortality in the cardiac intensive care unit (CICU) patients with CS.

Methods

Using a single-center database of CICU patients admitted between 2007 and 2015, we identified patients with an admission diagnosis of CS. MAP was measured every 15 min, and the mean of all MAP values during the first 24 h (mMAP24) was recorded. Multivariable logistic regression determined the relationship between mMAP24 and adjusted hospital mortality.

Results

We included 1002 patients with a mean age of 68 ± 13.7 years, including 36% females. Admission diagnoses included acute coronary syndrome in 60%, heart failure in 74%, and cardiac arrest in 38%. Vasoactive drugs were used in 72%. The mMAP24 was higher (75 vs. 71 mmHg, p < 0.001) among hospital survivors (66%) compared with non-survivors (34%). Hospital mortality was inversely associated with mMAP24 (adjusted OR 0.9 per 5 mmHg higher mMAP24, p = 0.01), with a stepwise increase in hospital mortality at lower mMAP24. Patients with mMAP24 < 65 mmHg were at higher risk of hospital mortality (57% vs. 28%, adjusted OR 2.0, 95% CI 1.4–3.0, p < 0.001); no differences were observed between patients with mMAP24 65–74 vs. ≥ 75 mmHg (p > 0.1).

Conclusion

In patients with CS, we observed an inverse relationship between mMAP24 and hospital mortality. The poor outcomes in patients with mMAP24 < 65 mmHg provide indirect evidence supporting a MAP goal of 65 mmHg for patients with CS.
Cis and trans effects differentially contribute to the evolution of promoters and enhancers
Authors: Mattioli Kaia , Oliveros Winona , Gerhardinger Chiara , Andergassen Daniel , Maass Philipp G. , Rinn John L. , Melé Marta
Published: August 2020

Background

Gene expression differences between species are driven by both cis and trans effects. Whereas cis effects are caused by genetic variants located on the same DNA molecule as the target gene, trans effects are due to genetic variants that affect diffusible elements. Previous studies have mostly assessed the impact of cis and trans effects at the gene level. However, how cis and trans effects differentially impact regulatory elements such as enhancers and promoters remains poorly understood. Here, we use massively parallel reporter assays to directly measure the transcriptional outputs of thousands of individual regulatory elements in embryonic stem cells and measure cis and trans effects between human and mouse.

Results

Our approach reveals that cis effects are widespread across transcribed regulatory elements, and the strongest cis effects are associated with the disruption of motifs recognized by strong transcriptional activators. Conversely, we find that trans effects are rare but stronger in enhancers than promoters and are associated with a subset of transcription factors that are differentially expressed between human and mouse. While we find that cis-trans compensation is common within promoters, we do not see evidence of widespread cis-trans compensation at enhancers. Cis-trans compensation is inversely correlated with enhancer redundancy, suggesting that such compensation may often occur across multiple enhancers.

Conclusions

Our results highlight differences in the mode of evolution between promoters and enhancers in complex mammalian genomes and indicate that studying the evolution of individual regulatory elements is pivotal to understand the tempo and mode of gene expression evolution.
Identifying disease trajectories with predicate information from a knowledge graph
Authors: Vlietstra Wytze J. , Vos Rein , van den Akker Marjan , van Mulligen Erik M. , Kors Jan A.
Published: August 2020

Background

Knowledge graphs can represent the contents of biomedical literature and databases as subject-predicate-object triples, thereby enabling comprehensive analyses that identify e.g. relationships between diseases. Some diseases are often diagnosed in patients in specific temporal sequences, which are referred to as disease trajectories. Here, we determine whether a sequence of two diseases forms a trajectory by leveraging the predicate information from paths between (disease) proteins in a knowledge graph. Furthermore, we determine the added value of directional information of predicates for this task. To do so, we create four feature sets, based on two methods for representing indirect paths, and both with and without directional information of predicates (i.e., which protein is considered subject and which object). The added value of the directional information of predicates is quantified by comparing the classification performance of the feature sets that include or exclude it.

Results

Our method achieved a maximum area under the ROC curve of 89.8% and 74.5% when evaluated with two different reference sets. Use of directional information of predicates significantly improved performance by 6.5 and 2.0 percentage points respectively.

Conclusions

Our work demonstrates that predicates between proteins can be used to identify disease trajectories. Using the directional information of predicates significantly improved performance over not using this information.
SPP1 promotes Schwann cell proliferation and survival through PKCα by binding with CD44 and αvβ3 after peripheral nerve injury
Authors: Wang Jiang-Bo , Zhang Zhan , Li Jian-Nan , Yang Tuo , Du Shuang , Cao Rang-Juan , Cui Shu-Sen
Published: August 2020

Background

Schwann cells (SCs) play a crucial role in Wallerian degeneration after peripheral nerve injury. The expression of genes in SCs undergo a series of changes, which greatly affect the proliferation and apoptosis of SCs as well as the fate of peripheral nerve regeneration. However, how do these genes regulate the proliferation and apoptosis of SCs remains unclear.

Results

SPP1 and PKCα were found upregulated after human median peripheral nerve injury, which promoted SCs proliferation and survival. The promoted proliferation and inhibited apoptosis by SPP1 were blocked after the treatment of PKCα antagonist Gö6976. Whereas, the inhibited proliferation and enhanced apoptosis induced by silence of SPP1 could be rescued by the activation of PKCα, which suggested that SPP1 functioned through PKCα. Moreover, both CD44 and αvβ3 were found expressed in SCs and increased after peripheral nerve injury. Silence of CD44 or β3 alleviated the increased proliferation and inhibited apoptosis induced by recombinant osteopontin, suggesting the function of SPP1 on SCs were dependent on CD44 and β3.

Conclusion

These results suggested that SPP1 promoted proliferation and inhibited apoptosis of SCs through PKCα signaling pathway by binding with CD44 and αvβ3. This study provides a potential therapeutic target for improving peripheral nerve recovery.
Trends and socioeconomic disparities in diabetes prevalence and quality of care among Israeli children; 2011-2018
Authors: Loewenberg Weisband Yiska , Krieger Michal , Calderon-Margalit Ronit , Manor Orly
Published: August 2020

Background

Despite Israel’s universal health coverage, disparities in health services provision may still exist. We aimed to assess socioeconomic disparities in diabetes prevalence and quality of care among Israeli children, and to assess whether these changed over time.

Methods

We used repeated cross-sectional analyses in the setting of the National Program for Quality Indicators in Community Healthcare. The data were derived from electronic medical records from Israel’s four health maintenance organizations. The study population included all Israeli children aged 2–17 years in 2011–2018 (2018: N = 2,404,856). Socio-economic position (SEP) was measured using Central Bureau of Statistics data further updated by a private company (Points Business Mapping Ltd), and grouped into 4 categories, ranging from 1 (lowest) to 4 (highest). We used logistic regression to assess the association of SEP with diabetes prevalence, diabetes clinic visits, hemoglobin A1C (HbA1C) testing, and poor glycemic control (HbA1c > 9%), and assessed whether these changed over time.

Results

Diabetes prevalence increased with age and SEP, with a total of 3019 children with diabetes. SEP was positively associated with visiting a specialized diabetes clinic (age and sex adjusted Odds Ratio (aORSEP 4 vs. 1 2.45, 95% Confidence Interval (CI) 1.67–3.69)). Although children in higher SEPs were less likely to undergo HbA1c testing (aORSEP 4 vs. 1 0.54, 95% CI 0.40–0.72), they were also less likely to have poor glycemic control (aORSEP 4 vs. 1 0.25, 95% CI 0.18–0.34). Disparities were especially apparent among children aged 2–9 (6.5% poor glycemic control in SEP 4 vs. 38.2% in SEP 1). Poor glycemic control decreased over time, from 44.0% in 2011 to 34.1% in 2018.

Conclusions

While poor glycemic control rates among children have improved, they remain high compared to rates in adults. Additionally, substantial socioeconomic gaps remain. It is eminent to study the causes of these disparities and develop policies to improve care provided to children in the lower SEP levels, to promote health equity.
On decay and blow-up of solutions for a nonlinear Petrovsky system with conical degeneration
Authors: Yu Jiali , Shang Yadong , Di Huafei
Published: August 2020

This paper deals with a class of Petrovsky system with nonlinear damping $$\begin{aligned} w_{tt}+\Delta _{\mathbb{B}}^{2}w-k_{2} \Delta _{\mathbb{B}}w_{t}+aw_{t} \vert w_{t} \vert ^{m-2}=bw \vert w \vert ^{p-2} \end{aligned}$$

w

t
t

+

Δ
B
2

w
−

k
2

Δ
B

w
t

+
a

w
t

|

w
t

|

m
−
2

=
b
w
|
w

|

p
−
2

on a manifold with conical singularity, where $\Delta _{\mathbb{B}}$

Δ
B

is a Fuchsian-type Laplace operator with totally characteristic degeneracy on the boundary $x_{1}=0$

x
1

=
0
. We first prove the global existence of solutions under conditions without relation between m and p, and establish an exponential decay rate. Furthermore, we obtain a finite time blow-up result for local solutions with low initial energy $E(0)< d$
E
(
0
)
<
d
.
CORE-OM as a routine outcome measure for adolescents with emotional disorders: factor structure and psychometric properties
Authors: Lorentzen Veronica , Handegård Bjørn Helge , Moen Connie Malén , Solem Kenth , Lillevoll Kjersti , Skre Ingunn
Published: August 2020

Background

Instruments for monitoring the clinical status of adolescents with emotional problems are needed. The Clinical Outcomes in Routine Evaluation-Outcome Measure (CORE-OM) according to theory measures problems/symptoms, well-being, functioning and risk. Documentation of whether the theoretical factor structure for CORE-OM is applicable for adolescents is lacking.

Methods

This study examined the factor structure and psychometric properties of the CORE-OM based on two samples of adolescents (age 14–18): youths seeking treatment for emotional problems (N = 140) and high school students (N = 531). A split half approach was chosen. An exploratory factor analysis (EFA) was performed on the first half of the stratified samples to establish the suitability of the model. A Confirmatory Factor Analysis (CFA) with the chosen model from the EFA was performed on the second half. Internal consistency and clinical cut-off scores of the CORE-OM were investigated.

Results

The best fitting model only partially confirmed the theoretical model for the CORE-OM. The model consisted of five factors: 1) General problems, 2) risk to self, 3) positive resources 4) risk to others and 5) problems with others. The clinical cut-off score based on the all-item total was higher than in an adult sample. Both the all-item total and general problems cut-off scores showed gender differences.

Conclusion

The factor analysis on CORE-OM for adolescents resulted in a five-factor solution, and opens up for new subscales concerning positive resources and problems with others. A 17-item solution for the general problems/symptoms scale is suggested. We advise developers of self-report instruments not to reverse items, if they do not intend to measure a separate factor, since these seem to affect the dimensionality of the scales. Comparing means for gender in non-clinical samples should not be done without modification of the general emotional problem and the positive resources scales. Slightly elevated CORE-OM scores (up to 1.3) in adolescents may be normal fluctuations.
Assessment of radial glia in the frontal lobe of fetuses with Down syndrome
Authors: Baburamani Ana A. , Vontell Regina T. , Uus Alena , Pietsch Maximilian , Patkee Prachi A. , Wyatt-Ashmead Jo , Chin-Smith Evonne C. , Supramaniam Veena G. , Donald Tournier J. , Deprez Maria , Rutherford Mary A.
Published: August 2020

Down syndrome (DS) occurs with triplication of human chromosome 21 and is associated with deviations in cortical development evidenced by simplified gyral appearance and reduced cortical surface area. Radial glia are neuronal and glial progenitors that also create a scaffolding structure essential for migrating neurons to reach cortical targets and therefore play a critical role in cortical development. The aim of this study was to characterise radial glial expression pattern and morphology in the frontal lobe of the developing human fetal brain with DS and age-matched controls. Secondly, we investigated whether microstructural information from in vivo magnetic resonance imaging (MRI) could reflect histological findings from human brain tissue samples. Immunohistochemistry was performed on paraffin-embedded human post-mortem brain tissue from nine fetuses and neonates with DS (15–39 gestational weeks (GW)) and nine euploid age-matched brains (18–39 GW). Radial glia markers CRYAB, HOPX, SOX2, GFAP and Vimentin were assessed in the Ventricular Zone, Subventricular Zone and Intermediate Zone. In vivo diffusion MRI was used to assess microstructure in these regions in one DS (21 GW) and one control (22 GW) fetal brain. We found a significant reduction in radial glial progenitor SOX2 and subtle deviations in radial glia expression (GFAP and Vimentin) prior to 24 GW in DS. In vivo, fetal MRI demonstrates underlying radial projections consistent with immunohistopathology. Radial glial alterations may contribute to the subsequent simplified gyral patterns and decreased cortical volumes observed in the DS brain. Recent advances in fetal MRI acquisition and analysis could provide non-invasive imaging-based biomarkers of early developmental deviations.
Ovine congenital progressive muscular dystrophy (OCPMD) is a model of TNNT1 congenital myopathy
Authors: Clayton Joshua S. , McNamara Elyshia L. , Goullee Hayley , Conijn Stefan , Muthsam Keren , Musk Gabrielle C. , Coote David , Kijas James , Testa Alison C. , Taylor Rhonda L. , O’Hara Amanda J. , Groth David , Ottenheijm Coen , Ravenscroft Gianina , Laing Nigel G. , Nowak Kristen J.
Published: August 2020

Ovine congenital progressive muscular dystrophy (OCPMD) was first described in Merino sheep flocks in Queensland and Western Australia in the 1960s and 1970s. The most prominent feature of the disease is a distinctive gait with stiffness of the hind limbs that can be seen as early as 3 weeks after birth. The disease is progressive. Histopathological examination had revealed dystrophic changes specifically in type I (slow) myofibres, while electron microscopy had demonstrated abundant nemaline bodies. Therefore, it was never certain whether the disease was a dystrophy or a congenital myopathy with dystrophic features. In this study, we performed whole genome sequencing of OCPMD sheep and identified a single base deletion at the splice donor site (+ 1) of intron 13 in the type I myofibre-specific TNNT1 gene (KT218690 c.614 + 1delG). All affected sheep were homozygous for this variant. Examination of TNNT1 splicing by RT-PCR showed intron retention and premature termination, which disrupts the highly conserved 14 amino acid C-terminus. The variant did not reduce TNNT1 protein levels or affect its localization but impaired its ability to modulate muscle contraction in response to Ca2+ levels. Identification of the causative variant in TNNT1 finally clarifies that the OCPMD sheep is in fact a large animal model of TNNT1 congenital myopathy. This model could now be used for testing molecular or gene therapies.
Effects of implant thread design on primary stability—a comparison between single- and double-threaded implants in an artificial bone model
Authors: Yamaguchi Yoko , Shiota Makoto , Fujii Masaki , Shimogishi Masahiro , Munakata Motohiro
Published: August 2020

Background

Primary implant stability is essential for osseointegration. To increase stability without changing the implant size, the thread length must be extended by reducing pitch, using a double-threaded implant, or reducing pitch/lead and lead angle to half that of a single-threaded implant.

Materials and methods

We tested the stabilities of these configurations using artificial bone. A 1.2-mm pitch, single-threaded implant (12S) was the control. We tested a 0.6-mm pitch/1.2-mm-lead double-threaded implant (06D) and a 0.6-mm pitch/lead single-threaded implant (06S). We compared stabilities by measuring insertion torque, removal torque, and the implant stability quotient (ISQ). Damage to bone tissue caused by the implants was evaluated using microscopy and morphometric analysis.

Results

We show that 06D and 06S significantly improved stability compared with the 12S reference. The stability of 06S was significantly greater compared with that of 06D, except for ISQ. The three implants were associated with bone tissue damage characterized by debris and voids surrounding the implant/bone interface. The 06D caused the most tissue damage, followed by 06S and then 12S.

Conclusion

These findings indicate that primary stability was significantly improved by changing the implant size, extending the thread length with reduced pitch/lead, and reducing the lead angle to half that of a single-threaded implant compared with a double-threaded implant.
Automatic lung segmentation in routine imaging is primarily a data diversity problem, not a methodology problem
Authors: Hofmanninger Johannes , Prayer Forian , Pan Jeanny , Röhrich Sebastian , Prosch Helmut , Langs Georg
Published: August 2020

Background

Automated segmentation of anatomical structures is a crucial step in image analysis. For lung segmentation in computed tomography, a variety of approaches exists, involving sophisticated pipelines trained and validated on different datasets. However, the clinical applicability of these approaches across diseases remains limited.

Methods

We compared four generic deep learning approaches trained on various datasets and two readily available lung segmentation algorithms. We performed evaluation on routine imaging data with more than six different disease patterns and three published data sets.

Results

Using different deep learning approaches, mean Dice similarity coefficients (DSCs) on test datasets varied not over 0.02. When trained on a diverse routine dataset (n = 36), a standard approach (U-net) yields a higher DSC (0.97 ± 0.05) compared to training on public datasets such as the Lung Tissue Research Consortium (0.94 ± 0.13, p = 0.024) or Anatomy 3 (0.92 ± 0.15, p = 0.001). Trained on routine data (n = 231) covering multiple diseases, U-net compared to reference methods yields a DSC of 0.98 ± 0.03 versus 0.94 ± 0.12 (p = 0.024).

Conclusions

The accuracy and reliability of lung segmentation algorithms on demanding cases primarily relies on the diversity of the training data, highlighting the importance of data diversity compared to model choice. Efforts in developing new datasets and providing trained models to the public are critical. By releasing the trained model under General Public License 3.0, we aim to foster research on lung diseases by providing a readily available tool for segmentation of pathological lungs.
High fat diet accelerates and exacerbates microgliosis and neuronal damage/death in the somatosensory cortex after transient forebrain ischemia in gerbils
Authors: Seo Won Joo , Ahn Ji Hyeon , Lee Tae-Kyeong , Kim Bora , Lee Jae-Chul , Park Joon Ha , Yoo Yeon Ho , Shin Myoung Cheol , Cho Jun Hwi , Won Moo-Ho , Park Yoonsoo
Published: August 2020

Obesity has been known as an independent risk factor for stroke. Effects of high-fat diet (HFD)-induced obesity on neuronal damage in the somatosensory cortex of animal models of cerebral ischemia have not been studied yet. In this study, HFD-induced obesity was used to study the impact of obesity on neuronal damage/loss and microgliosis in the somatosensory cortex of a gerbil model of 5-min transient forebrain ischemia. We used gerbils fed normal diet (ND) and HFD and chronologically examined microgliosis (microglial cell activation) by ionized calcium-binding adapter molecule 1 (Iba-1) immunohistochemistry. In addition, we examined neuronal damage or death by using neuronal nuclear protein (NeuN, a neuronal marker) immunohistochemistry and Fluoro-Jade B (F-J B, a marker for neuronal degeneration) histofluorescence staining. We found that ischemia-induced microgliosis in ND-fed gerbils was increased from 2 days post-ischemia; however, ischemia-mediated microgliosis in HFD-fed gerbils increased from 1 day post-ischemia and more accelerated with time than that in the ND-fed gerbils. Ischemia-induced neuronal death/loss in the somatosensory cortex in the ND-fed gerbils was apparently found at 5 days post-ischemia. However, in the HFD-fed gerbils, neuronal death/loss was shown from 2 days post-ischemia and progressively exacerbated at 5 days post-ischemia. Our findings indicate that HFD can evoke earlier microgliosis and more detrimental neuronal death/loss in the somatosensory cortex after transient ischemia than ND evokes.
The effect of hyperlactatemia timing on the outcomes after cardiac surgery
Authors: Algarni Khaled D.
Published: August 2020

Background

Several studies linked postoperative hyperlactatemia to worse outcomes in adult patients undergoing cardiac surgery. However, data on the effect of timing of hyperlactatemia on outcomes are scarce. We sought to determine the prevalence of early hyperlactatemia (EHL) and its impact on clinical outcomes compared to late hyperlactatemia (LHL) in patients undergoing ACS procedures.

Results

We included 305 consecutive adult patients who underwent cardiac surgery procedures between July 2017 and Nov 2019 at a single institution. Lactate level was measured in the first 10 h after surgery and EHL was defined as lactate level > 3 mmol/L in the first hour after surgery. Logistic regression analysis was performed to determine predictors of EHL. Seventeen percent (n= 52) had EH while 83% (n= 253) did not. Patients with EHL had significantly longer cardiopulmonary bypass (P= 0.001) and cross-clamp (P= 0.001) times due to increased surgical complexity in this group. Early hyperlactatemia was associated with increased post-operative extracorporeal membrane oxygenation (ECMO) support (0% vs 5.7%,P< 0.001), longer intensive care unit stay (P= 0.004), and increased hospital mortality (0% vs. 3.8%,P= 0.009). Cardiopulmonary bypass time (OR 1.001; 95% CI 1.011–1.012,P= 0.02) and glucose level (OR 1.2; 95% CI 1.1–1.3,P= 0.003) were independently associated with increased rate of EHL. In contrast, diabetes mellitus (OR 0.26; 95% CI 0.12–0.55,P< 0.001) significantly attenuated the rate of EHL.

Conclusions

Early hyperlactatemia after cardiac surgery was associated with increased morbidity and mortality. Late hyperlactatemia was very common and had a self-limiting and benign course.
Mean platelet volume change (∆MPV) and red blood cell distribution width (RDW) as promising markers of community-acquired pneumonia (CAP) outcome
Authors: Farghly Sahar , Abd-Elkader Randa , El Zohne Randa A. , Abd El-Kareem Doaa M.
Published: August 2020

Background

Prognostic markers play an essential role in the proper management of community-acquired pneumonia. This research work aimed to evaluate the association of RDW and /or MPV with mortality and morbidity in patients with CAP to improve the yield of already used prognostic scores.

Results

The current study enrolled 153 patients with community-acquired pneumonia (CAP). Out of them, 101 (64%) patients improved while 52 (36%) died. It was noticed that each of delta MPV and RDW (P < 0.001) had positive significant correlation with PSI and CURB-65. Delta MPV and RDW was significantly higher in patients who died (2.61 ± 1.01 vs. 1.78 ± 0.76; P = 0.01 for delta MPV and 16.50 ± 3.54 vs. 15.50 ± 2.81; P = 0.02 for RDW).

Conclusion

Initial RDW and rising MPV during hospitalization for CAP is associated with more severe clinical characteristics and high mortality. Moreover, the use of RDW and delta MPV in patients admitted with CAP can improve the performance of prognostic scales.
Digital Tumor Board Solutions Have Significant Impact on Case Preparation
Authors: Hammer Richard D. , Fowler Donna , Sheets Lincoln R. , Siadimas Athanasios , Guo Chaohui , Prime Matthew S.
Published: August 2020

PURPOSE

Multidisciplinary tumor boards (TBs) are the gold standard for decision-making in cancer care. Variability in preparation, conduction, and impact is widely reported. The benefit of digital technologies to support TBs is unknown. This study evaluated the impact of the NAVIFY Tumor Board solution (NTB) on TB preparation time across multiple user groups in 4 cancer categories: breast, GI, head and neck (ie, ear, nose, and throat, or ENT), and hematopathology.

METHODS

This prospective study evaluated TB preparation time in multiple phases pre- and post-NTB implementation at an academic health care center. TB preparation times were recorded for multiple weeks using a digital time tracker.

RESULTS

Preparation times for 59 breast, 61 GI, 36 ENT, and 71 hematopathology cancer TBs comparing a pre-NTB phase to 3 phases of NTB implementation were evaluated between February 2018 and July 2019. NTB resulted in significant reductions in overall preparation time (30%) across 3 TBs pre-NTB compared with the final post-NTB implementation phase. In the breast TB, NTB reduced overall preparation time by 28%, with a 76% decrease in standard deviation (SD). In the GI TB, a 23% reduction in average preparation time was observed for all users, with a 48% decrease in SD. In the ENT TB, a 33% reduction in average preparation time was observed for all users, with a 73% decrease in SD. The hematopathology TB, which was the cocreation partner and initial adopter of the solution, showed variable results.

CONCLUSION

This study showed a significant impact of a digital solution on time preparation for TBs across multiple users and different TBs, reflecting the generalizability of the NTB. Adoption of such a solution could improve the efficiency of TBs and have a direct economic impact on hospitals.
Long-Term Outcomes of Laparoscopic Distal Gastrectomy for Locally Advanced Gastric Cancer: The KLASS-02-RCT Randomized Clinical Trial
Authors: Hyung Woo Jin , Yang Han-Kwang , Park Young-Kyu , Lee Hyuk-Joon , An Ji Yeong , Kim Wook , Kim Hyoung-Il , Kim Hyung-Ho , Ryu Seung Wan , Hur Hoon , Kim Min-Chan , Kong Seong-Ho , Cho Gyu Seok , Kim Jin-Jo , Park Do Joong , Ryu Keun Won , Kim Young Woo , Kim Jong Won , Lee Joo-Ho , Han Sang-Uk ,   on behalf of the Korean Laparoendoscopic Gastrointestinal Surgery Study Group
Published: August 2020

PURPOSE

It is unclear whether laparoscopic distal gastrectomy for locally advanced gastric cancer is oncologically equivalent to open distal gastrectomy. The noninferiority of laparoscopic subtotal gastrectomy with D2 lymphadenectomy for locally advanced gastric cancer compared with open surgery in terms of 3-year relapse-free survival rate was evaluated.

PATIENTS AND METHODS

A phase III, open-label, randomized controlled trial was conducted for patients with histologically proven locally advanced gastric adenocarcinoma suitable for distal subtotal gastrectomy. The primary end point was the 3-year relapse-free survival rate; the upper limit of the hazard ratio (HR) for noninferiority was 1.43 between the laparoscopic and open distal gastrectomy groups.

RESULTS

From November 2011 to April 2015, 1,050 patients were randomly assigned to laparoscopy (n = 524) or open surgery (n = 526). After exclusions, 492 patients underwent laparoscopic surgery and 482 underwent open surgery and were included in the analysis. The laparoscopy group, compared with the open surgery group, suffered fewer early complications (15.7% v 23.4%, respectively; P = .0027) and late complications (4.7% v 9.5%, respectively; P = .0038), particularly intestinal obstruction (2.0% v 4.4%, respectively; P = .0447). The 3-year relapse-free survival rate was 80.3% (95% CI, 76.0% to 85.0%) for the laparoscopy group and 81.3% (95% CI, 77.0% to 85.0%; log-rank P = .726) for the open group. Cox regression analysis after stratification by the surgeon revealed an HR of 1.035 (95% CI, 0.762 to 1.406; log-rank P = .827; P for noninferiority = .039). When stratified by pathologic stage, the HR was 1.020 (95% CI, 0.751 to 1.385; log-rank P = .900; P for noninferiority = .030).

CONCLUSION

Laparoscopic distal gastrectomy with D2 lymphadenectomy was comparable to open surgery in terms of relapse-free survival for patients with locally advanced gastric cancer. Laparoscopic distal gastrectomy with D2 lymphadenectomy could be a potential standard treatment option for locally advanced gastric cancer.