bluuebunny/crossref_metadata_2025 huggingface dataset:
Establishment and optimization of mRNA in situ hybridization system in turnip (Brassica rapa var. rapa)
Authors: Li Cheng , Hu Simin , Lei Qidong , Wang Chongde , Yang Yunqiang , Yang Yongping , Sun Xudong
Published: October 2019

Background

In situ hybridization (ISH) is a general molecular biological technique used to determine the spatiotemporal expression of genes in many species. In the past few years, numerous ISH protocols have been established in many species. Turnip (Brassica rapa var. rapa) is an important crop in the world, especially in the Plateau area of China, and is a traditional Tibetan medicine. However, ISH protocol in turnip has not been established.

Results

We explored and established an optimal workflow for mRNA ISH system for turnip which has been evaluated using BrrCLV3 and BrrWUSa. The optimal methods include: (1) fixation method, (2) protease K pretreatment time, (3) probe length and concentration, (4) washing temperature. We also provide advice on weakening background and improving the efficiency of RNA transcription in vitro. The expression of the BrrCLV3 gene in turnip was detected by the optimized system, and the applicability of the system was confirmed by using BrrWUSa.

Conclusions

In this study, we established and optimized the mRNA ISH system for turnip. We explored and found that (1) FAA fixative was the optimized fixation method, (2) 30 min was the optimized protease K pretreatment time, (3) 100 bp, 100 ng/ml probe had good hybridization signal, (4) the optimized washing temperature was 52 °C. It provides a powerful method to locate mRNA in the tissue, which can study the expression and function of turnip’s genes. As such, it has considerable advantages in terms of time and cost.
Assessing the Integrated Community-Based Health Systems Strengthening initiative in northern Togo: a pragmatic effectiveness-implementation study protocol
Authors: Lauria Molly E. , Fiori Kevin P. , Jones Heidi E. , Gbeleou Sesso , Kenkou Komlan , Agoro Sibabe , Agbèrè Abdourahmane Diparidé , Lue Kelly D. , Hirschhorn Lisa R.
Published: October 2019

Background

Over the past decade, prevalence of maternal and child morbidity and mortality in Togo, particularly in the northern regions, has remained high despite global progress. The causes of under-five child mortality in Togo are diseases with effective and low-cost prevention and/or treatment strategies, including malaria, acute lower respiratory infections, and diarrheal diseases. While Togo has a national strategy for implementing the integrated management of childhood illness (IMCI) guidelines, including a policy on integrated community case management (iCCM), challenges in implementation and low public sector health service utilization persist. There are critical gaps to access and quality of community health systems throughout the country. An integrated facility- and community-based initiative, the Integrated Community-Based Health Systems Strengthening (ICBHSS) initiative, seeks to address these gaps while strengthening the public sector health system in northern Togo. This study aims to evaluate the effect and implementation strategy of the ICBHSS initiative over 48 months in the catchment areas of 21 public sector health facilities.

Methods

The ICBHSS model comprises a bundle of evidence-based interventions targeting children under five, women of reproductive age, and people living with HIV through (1) community engagement and feedback; (2) elimination of point-of-care costs; (3) proactive community-based IMCI using community health workers (CHWs) with additional services including family planning, HIV testing, and referrals; (4) clinical mentoring and enhanced supervision; and (5) improved supply chain management and facility structures. Using a pragmatic type II hybrid effectiveness-implementation study, we will evaluate the ICBHSS initiative with two primary aims: (1) determine effectiveness through changes in under-five mortality rates and (2) assess the implementation strategy through measures of reach, adoption, implementation, and maintenance. We will conduct a mixed-methods assessment using the RE-AIM (reach, effectiveness, adoption, implementation, maintenance) framework. This assessment consists of four components: (1) a stepped-wedge cluster randomized control trial using a community-based household survey, (2) annual health facility assessments, (3) key informant interviews, and (4) costing and return-on-investment assessments for each randomized cluster.

Discussion

Our research is expected to contribute to continuous quality improvement initiatives, optimize implementation factors, provide knowledge regarding health service delivery, and accelerate health systems improvements in Togo and more broadly.

Trial registration

ClinicalTrials.gov,NCT03694366, registered 3 October 2018
Elective nodal irradiation versus involved-field irradiation in patients with esophageal cancer receiving neoadjuvant chemoradiotherapy: a network meta-analysis
Authors: Liu Tingting , Ding Silu , Dang Jun , Wang Hui , Chen Jun , Li Guang
Published: October 2019

Background

To assess the comparative efficacy and safety of elective nodal irradiation (ENI) and involved-field irradiation (IFI) in patients with esophageal cancer (EC) receiving neoadjuvant chemoradiotherapy plus surgery (nCRTS).

Material and methods

PubMed, Embase, Cochrane Library, Web of Science and major meetings were searched for randomized controlled trials (RCTs) that compared at least two of the following treatment regimens: nCRTS, neoadjuvant chemotherapy plus surgery (nCTS), and surgery (S) alone. Overall survival (OS) was the primary outcomes of interest, reported as hazard ratio (HR) and 95% confidence intervals (CIs). A Bayesian network meta-analysis was performed to compare all regimens simultaneously.

Results

Twenty-nine RCTs with a total of 5212 patients were included in the meta-analysis. Both nCRTS adopting ENI (nCRTS-ENI) (HR = 0.63, 95% CI: 0.48–0.83) and nCRTS adopting IFI (nCRTS-IFI) (HR = 0.75, 95% CI: 0.66–0.86) significantly improved OS compared to S alone. No significant differences in OS, locoregional recurrence, distant metastases, R0 resection and postoperative mortality were observed between nCRTS-ENI and nCRTS-IFI. In subgroup analyses, nCRTS-IFI showed a significant OS advantage over nCTS (HR = 0.78, 95% CI: 0.63–0.96) and S alone (HR = 0.50, 95% CI: 0.38–0.68) for esophagus squamous cell carcinoma (ESCC), but nCRTS-ENI did not; nCRTS-ENI using three-dimensional radiotherapy (3D-RT) resulted in an improved OS compared to that with 2D-RT (HR = 0.58, 95% CI: 0.34–0.99). Based on treatment ranking in term of OS, nCRTS-IFI (0.90) and nCRTS-ENI (0.96) was ranked the most effective treatment for ESCC and esophagus adenocarcinoma (EAC), respectively.

Conclusion

Either adopting ENI or IFI, nCRTS is likely to be the optimal treatment for resectable EC, and nCRTS-IFI and nCRTS-ENI seem to be more effective for patients with ESCC and EAC, respectively. Future head to head comparison trials are needed to confirm these findings.
Correction to: Ethical considerations in conducting surgical research in severe complicated intra-abdominal sepsis
Authors:   Closed Or Open after Laparotomy (COOL) after Source Control for Severe Complicated Intra-Abdominal Sepsis Investigators, Doig Christopher J. , Page Stacey A. , McKee Jessica L. , Moore Ernest E. , Abu-Zidan Fikri M. , Carroll Rosemary , Marshall John C. , Faris Peter D. , Tolonen Matti , Catena Fausto , Coccolini Federico , Sartelli Massimo , Ansaloni Luca , Minor Sam F. , Peirera Bruno M. , Diaz Jose J. , Kirkpatrick Andrew W.
Published: October 2019

The original article [1] contained a typo in author, Federico Coccolini’s name. This has now been corrected.
Exposure to family and organized violence and associated mental health in north Korean refugee youth compared to south Korean youth
Authors: Park Jinme , Catani Claudia , Hermenau Katharin , Elbert Thomas
Published: October 2019

Background

Studies on populations affected by organized violence have shown elevated levels of family violence against children. This form of violence has been found to contribute to children’s psychopathology independently of traumatic experiences related to war, persecution or flight. Little is known, so far, about the exposure to family violence and its relation to mental health in North Korean refugee youth affected by political violence. The aim of this study was to examine the amount of organized and family violence and associated psychopathology in a sample of North Korean refugee youth living in South Korea compared to their South Korean peers.

Methods

Sixty-five North Korean refugee youth and 65 South Korean youth were recruited. Trained researchers conducted the survey in group meetings of five to ten participants. Using questionnaires researchers assessed traumatic experiences, family and organized violence, PTSD symptoms, depressive symptoms and other mental health problems.

Results

Higher rates of violence and trauma, and higher levels of mental health problems were found in the North Korean sample compared to the South Korean sample. Linear regression analyses including the various types of trauma as potential predictors showed that the severity of PTSD and depressive symptoms in the North Korean sample were associated with the amount of traumatic events and family violence but not with higher levels of organized violence.

Conclusions

The findings suggest that in a context of organized violence, abusive experiences by family members constitute an important problem that is strongly linked to the psychopathology of adolescents. Our data suggest that psychological treatment and prevention approaches for North Korean refugees should be carefully tailored to fit the specific requirements of this population and address the mental health of the individual as well as potential problems at the family level.
NANOG helps cancer cells escape NK cell attack by downregulating ICAM1 during tumorigenesis
Authors: Saga Kotaro , Park Jinhee , Nimura Keisuke , Kawamura Norihiko , Ishibashi Airi , Nonomura Norio , Kaneda Yasufumi
Published: October 2019

Background

At the beginning of tumorigenesis, newly born cancer cells must successfully avoid attack by the immune system. Although most abnormal cells are efficiently identified and destroyed by the immune system, particularly by NK cells, the molecular mechanisms by which newly born cancer cells evade NK cell surveillance are not fully understood.

Methods

NK cell resistance of highly tumorigenic population of human prostate cancer (PCa) cells were confirmed by xenograft in SCID mice with or without NK cell neutralization. The mechanisms by which the tumorigenic PCa cells evaded NK cell attack were investigated by RNAseq, ChIPseq, generation of several transformants and xenograft in SCID mice.

Results

Here, we show that PCa cells have a strengthened ability to escape NK cell attack due to NANOG, a pluripotent-related transcription factor, mediating the repression of ICAM1, a cell adhesion molecule, during tumorigenesis. Mechanistically, NANOG directly binds to the region upstream ofICAM1. As the binding between NANOG and the upstreamICAM1region increases, p300 binding to this region is diminished, resulting in decreased ICAM1 expression. High NANOG expression confers PCa cells the ability to resist NK cell attack via the repression of ICAM1. Consistent with these results, lowICAM1expression is significantly correlated with a high recurrence rate in patients with PCa.

Conclusions

Our findings indicate that repression of ICAM1 is a critical mechanism by which cancer cells evade attack from NK cells during tumorigenesis. These results suggest a pivotal role of NANOG in establishing a gene expression profile for escaping the immune system.
Long non-coding RNAs identify a subset of luminal muscle-invasive bladder cancer patients with favorable prognosis
Authors: de Jong Joep J. , Liu Yang , Robertson A. Gordon , Seiler Roland , Groeneveld Clarice S. , van der Heijden Michiel S. , Wright Jonathan L. , Douglas James , Dall’Era Marc , Crabb Simon J. , van Rhijn Bas W. G. , van Kessel Kim E. M. , Davicioni Elai , Castro Mauro A. A. , Lotan Yair , Zwarthoff Ellen C. , Black Peter C. , Boormans Joost L. , Gibb Ewan A.
Published: October 2019

Background

Muscle-invasive bladder cancer (MIBC) is a heterogeneous disease, and gene expression profiling has identified several molecular subtypes with distinct biological and clinicopathological characteristics. While MIBC subtyping has primarily been based on messenger RNA (mRNA), long non-coding RNAs (lncRNAs) may provide additional resolution.

Methods

LncRNA expression was quantified from microarray data of a MIBC cohort treated with neoadjuvant chemotherapy (NAC) and radical cystectomy (RC) (n = 223). Unsupervised consensus clustering of highly variant lncRNAs identified a four-cluster solution, which was characterized using a panel of MIBC biomarkers, regulon activity profiles, gene signatures, and survival analysis. The four-cluster solution was confirmed in The Cancer Genome Atlas (TCGA) cohort (n = 405). A single-sample genomic classifier (GC) was trained using ridge-penalized logistic regression and validated in two independent cohorts (n = 255 andn = 94).

Results

NAC and TCGA cohorts both contained an lncRNA cluster (LC3) with favorable prognosis that was enriched with tumors of the luminal-papillary (LP) subtype. In both cohorts, patients with LP tumors in LC3 (LPL-C3) were younger and had organ-confined, node-negative disease. The LPL-C3 tumors had enhanced FGFR3, SHH, and wild-type p53 pathway activity. In the TCGA cohort, LPL-C3 tumors were enriched forFGFR3mutations and depleted forTP53andRB1mutations. A GC trained to identify these LPL-C3 patients showed robust performance in two validation cohorts.

Conclusions

Using lncRNA expression profiles, we identified a biologically distinct subgroup of luminal-papillary MIBC with a favorable prognosis. These data suggest that lncRNAs provide additional information for higher-resolution subtyping, potentially improving precision patient management.
JAG2/Notch2 inhibits intervertebral disc degeneration by modulating cell proliferation, apoptosis, and extracellular matrix
Authors: Long Jun , Wang Xiaobo , Du Xianfa , Pan Hehai , Wang Jianru , Li Zemin , Liu Hui , Li Xudong , Zheng Zhaomin
Published: October 2019

Background

Intervertebral disc degeneration (IVDD)-related disorders are the major causes of low back pain. A previous study suggested that Notch activation serves as a protective mechanism and is a part of the compensatory response that maintains the necessary resident nucleus pulposus (NP) cell proliferation to replace lost or non-functional cells. However, the exact mechanism remains to be determined. In this study, we aimed to investigate the role of JAG2/Notch2 in NP cell proliferation and apoptosis.

Methods

Recombinant JAG2 or Notch2, Hes1, and Hey2 siRNAs were used to activate or inhibit Notch signaling. Cell proliferation, apoptosis, cell cycle regulatory factors, and pathways associated with Notch-mediated proliferation were examined. In vivo experiments involving an intradiscal injection of Sprague-Dawley rats were performed.

Results

Recombinant JAG2 induced Notch2 and Hes1/Hey2 expression together with NP cell proliferation. Downregulation of Notch2/Hes1/Hey2 induced G0/G1 phase cell cycle arrest in NP cells. Moreover, Notch2 mediated NP cell proliferation by regulating cyclin D1 and by activating PI3K/Akt and Wnt/β-catenin signaling. Furthermore, Notch signaling inhibited TNF-α-promoted NP cell apoptosis by suppressing the formation of the RIP1-FADD-caspase-8 complex. Finally, we found that intradiscal injection of JAG2 alleviated IVDD and that sh-Notch2 aggravated IVDD in a rat model. These results indicated that JAG2/Notch2 inhibited IVDD by modulating cell proliferation, apoptosis, and extracellular matrix. The JAG2/Notch2 axis regulated NP cell proliferation via PI3K/Akt and Wnt/β-catenin signaling and inhibited TNF-α-induced apoptosis by suppressing the formation of the RIP1-FADD-caspase-8 complex.

Conclusions

The current and previous results shed light on the therapeutic implications of targeting the JAG2/Notch2 axis to inhibit or reverse IVDD.
Mobile phone applications and their use in the self-management of Type 2 Diabetes Mellitus: a qualitative study among app users and non-app users
Authors: Jeffrey Bronte , Bagala Melina , Creighton Ashley , Leavey Tayla , Nicholls Sarah , Wood Crystal , Longman Jo , Barker Jane , Pit Sabrina
Published: October 2019

Background

Mobile phone applications (apps) have been shown to successfully facilitate the self-management of chronic disease. This study aims to evaluate firstly the experiences, barriers and facilitators to app usage among people with Type 2 Diabetes Mellitus (T2DM) and secondly determine recommendations to improve usage of diabetes apps.

Methods

Participants were aged ≥ 18 years with a diagnosis of T2DM for ≥ 6 months. Semi-structured phone-interviews were conducted with 16 app and 14 non-app users. Interviews were based on the Technology Acceptance Model, Health Information Technology Acceptance Model (HITAM) and the Mobile Application Rating Scale. Data were analysed using deductive content analysis.

Results

Most app-users found apps improved their T2DM self-management and health. The recommendation of apps by health professionals, as well as positive interactions with them, improved satisfaction; however, only a minority of patients had practitioners involved in their app use. All non-app users had never had the concept discussed with them by a health professional. Facilitators to app use included the visual representation of trends, intuitive navigation and convenience (for example, discretion and portability). Barriers to app use were participant’s lack of knowledge and awareness of apps as healthcare tools, perceptions of disease severity, technological and health literacy or practical limitations such as rural connectivity. Factors contributing to app use were classified into a framework based on the Health Belief Model and HITAM. Recommendations for future app design centred on educational features, which were currently lacking (e.g. diabetes complications, including organ damage and hypoglycaemic episodes), monitoring and tracking features (e.g. blood glucose level monitoring with trends and dynamic tips and comorbidities) and nutritional features (e.g. carbohydrate counters). Medication reminders were not used by participants. Lastly, participants felt that receiving weekly text-messaging relating to their self-management would be appropriate.

Conclusions

The incorporation of user-centred features, which engage T2DM consumers in self-management tasks, can improve health outcomes. The findings may guide app developers and entrepreneurs in improving app design and usability. Given self-management is a significant factor in glycaemic control, these findings are significant for GPs, nurse practitioners and allied health professionals who may integrate apps into a holistic management plan which considers strategies outside the clinical environment.
Intraportally delivered stem cell spheroids localize in the liver and protect hepatocytes against GalN/LPS-induced fulminant hepatic toxicity
Authors: Regmi Shobha , Pathak Shiva , Thanh Tung Pham , Nguyen Tiep Tien , Sung Jong-Hyuk , Yook Simmyung , Kim Jong Oh. , Yong Chul Soon , Choi Inho , Doh Kyoung-Oh , Park Pil-Hoon , Park Jun-Beom , Seo Yoojin , Kim Bieong-Kil , Lee Dong-Mok , Moon Ik-Jae , Kim Hyung-Sik , Jeong Jee-Heon
Published: October 2019

Background

Systemic inflammatory response syndrome (SIRS) is common in severe fulminant hepatic failure (FHF) and has a high mortality rate (20–50%) due to irreversible cerebral edema or sepsis. Stem cell-based treatment has emerged as a promising alternative therapeutic strategy to prolong the survival of patients suffering from FHF via the inhibition of SIRS due to their immunomodulatory effects.

Methods

3D spheroids of adipose-derived mesenchymal stem cells (3D-ADSC) were prepared by the hanging drop method. The efficacy of the 3D-ADSC to rescue FHF was evaluated in ad-galactosamine/lipopolysaccharide (GalN/LPS)-induced mouse model of FHF via intraportal transplantation of the spheroids.

Results

Intraportally delivered 3D-ADSC better engrafted and localized into the damaged livers compared to 2D-cultured adipose-derived mesenchymal stem cells (2D-ADSC). Transplantation of 3D-ADSC rescued 50% of mice from FHF-induced lethality, whereas only 20% of mice survived when 2D-ADSC were transplanted. The improved transplantation outcomes correlated with the enhanced immunomodulatory effect of 3D-ADSC in the liver microenvironment.

Conclusion

The study shows that the transplantation of optimized 3D-ADSC can efficiently ameliorate GalN/LPS-induced FHF due to improved viability, resistance to exogenous ROS, and enhanced immunomodulatory effects of 3D-ADSC.
Use of MIRUS™ for MAC-driven application of isoflurane, sevoflurane, and desflurane in postoperative ICU patients: a randomized controlled trial
Authors: Bellgardt Martin , Georgevici Adrian Iustin , Klutzny Mitja , Drees Dominik , Meiser Andreas , Gude Philipp , Vogelsang Heike , Weber Thomas Peter , Herzog-Niescery Jennifer
Published: October 2019

Background

The MIRUS™ (TIM, Koblenz, Germany) is an electronical gas delivery system, which offers an automated MAC (minimal alveolar concentration)-driven application of isoflurane, sevoflurane, or desflurane, and can be used for sedation in the intensive care unit. We investigated its consumption of volatile anesthetics at 0.5 MAC (primary endpoint) and the corresponding costs. Secondary endpoints were the technical feasibility to reach and control the MAC automatically, the depth of sedation at 0.5 MAC, and awakening times. Mechanically ventilated and sedated patients after major surgery were enrolled. Upon arrival in the intensive care unit, patients obtained intravenous propofol sedation for at least 1 h to collect ventilation and blood gas parameters, before they were switched to inhalational sedation using MIRUS™ with isoflurane, sevoflurane, or desflurane. After a minimum of 2 h, inhalational sedation was stopped, and awakening times were recorded. A multivariate electroencephalogram and the Richmond Agitation Sedation Scale (RASS) were used to assess the depth of sedation. Vital signs, ventilation parameters, gas consumption, MAC, and expiratory gas concentrations were continuously recorded.

Results

Thirty patients obtained inhalational sedation for 18:08 [14:46–21:34] [median 1st–3rd quartiles] hours. The MAC was 0.58 [0.50–0.64], resulting in a Narcotrend Index of 37.1 [30.9–42.4] and a RASS of − 3.0 [− 4.0 to (− 3.0)]. The median gas consumption was significantly lowest for isoflurane ([ml h−1]: isoflurane: 3.97 [3.61–5.70]; sevoflurane: 8.91 [6.32–13.76]; and desflurane: 25.88 [20.38–30.82]; p < 0.001). This corresponds to average costs of 0.39 € h−1 for isoflurane, 2.14 € h−1 for sevoflurane, and 7.54 € h−1 for desflurane. Awakening times (eye opening [min]: isoflurane: 9:48 [4:15–20:18]; sevoflurane: 3:45 [0:30–6:30]; desflurane: 2:00 [1:00–6:30]; p = 0.043) and time to extubation ([min]: isoflurane: 10:10 [8:00–20:30]; sevoflurane: 7:30 [4:37–14:22]; desflurane: 3:00 [3:00–6:00]; p = 0.007) were significantly shortest for desflurane.

Conclusions

A target-controlled, MAC-driven automated application of volatile anesthetics is technically feasible and enables an adequate depth of sedation. Gas consumption was highest for desflurane, which is also the most expensive volatile anesthetic. Although awakening times were shortest, the actual time saving of a few minutes might be negligible for most patients in the intensive care unit. Thus, using desflurane seems not rational from an economic perspective.

Trial registration Clinical Trials Registry (ref.: NCT03860129). Registered 24 September 2018—Retrospectively registered.
Link prediction in paper citation network to construct paper correlation graph
Authors: Liu Hanwen , Kou Huaizhen , Yan Chao , Qi Lianyong
Published: October 2019

Nowadays, recommender system has become one of the main tools to search for users’ interested papers. Since one paper often contains only a part of keywords that a user is interested in, recommender system returns a set of papers that satisfy the user’s need of keywords. Besides, to satisfy the users’ requirements of further research on a certain domain, the recommended papers must be correlated. However, each paper of an existing paper citation network hardly has cited relationships with others, so the correlated links among papers are very sparse. In addition, while a mass of research approaches have been put forward in terms of link prediction to address the network sparsity problems, these approaches have no relationship with the effect of self-citations and the potential correlations among papers (i.e., these correlated relationships are not included in the paper citation network as their published time is close). Therefore, we propose a link prediction approach that combines time, keywords, and authors’ information and optimizes the existing paper citation network. Finally, a number of experiments are performed on the real-world Hep-Th datasets. The experimental results demonstrate the feasibility of our proposal and achieve good performance.
A comparison between two recommendations to conduct and report systematic reviews on drug’s safety
Authors: Penedones Ana , Alves Carlos , Batel Marques Francisco
Published: October 2019

Background

Several recommendations are available to conduct and report a systematic review of adverse drug reactions. This study is aimed at identifying and comparing the methodologies of the two most commonly used recommendations to conduct and report systematic reviews on drug’s safety.

Methods

Two systematic reviews were conducted following the recommendations “Cochrane Handbook for Systematic Reviews of Interventions” and “Systematic Reviews’ Centre for Reviews and Dissemination guidance for undertaking reviews in healthcare.” The methods of each recommendation were characterized, and the results and the discussion of each systematic review were also evaluated.

Results

The methodologies of both recommendations are similar. The review question was structured. Both recommendations suggest to include pre- and post-marketing data. The recommended data sources differed and, consequently, the results of the systematic reviews (37 vs. 35 studies). Other aspects of search literature were identical. Different tools are suggested to evaluate the methodological quality of the included studies. For case reports, both recommendations only report some questions that may be helpful to assess risk of bias. The reporting of the results and discussion is also identical for both recommendations.

Conclusions

Few methodological differences were observed between the analyzed recommendations to conduct a systematic review on drug’s safety. Combining their methods into a single and recognized recommendation could be of great value.
Existence and exponential stability in the pth moment for impulsive neutral stochastic integro-differential equations driven by mixed fractional Brownian motion
Authors: Zhou Xia , Zhou Dongpeng , Zhong Shouming
Published: October 2019

This paper consider the existence, uniqueness and exponential stability in the pth moment of mild solution for impulsive neutral stochastic integro-differential equations driven simultaneously by fractional Brownian motion and by standard Brownian motion. Based on semigroup theory, the sufficient conditions to ensure the existence and uniqueness of mild solutions are obtained in terms of fractional power of operators and Banach fixed point theorem. Moreover, the pth moment exponential stability conditions of the equation are obtained by means of an impulsive integral inequality. Finally, an example is presented to illustrate the effectiveness of the obtained results.
A note on singular integrals with angular integrability
Authors: Liu Feng
Published: October 2019

In this note we study the rough singular integral
$$ T_{\varOmega }f(x)=\mathrm{p.v.} \int _{\mathbb{R}^{n}}f(x-y)\frac{\varOmega (y/ \vert y \vert )}{ \vert y \vert ^{n}}\,dy, $$

T
Ω

f
(
x
)
=

p
.
v
.

∫

R
n

f
(
x
−
y
)

Ω
(
y
/
|
y
|
)

|
y

|
n

d
y
,
where $n\geq 2$
n
≥
2
and Ω is a function in $L\log L(\mathrm{S} ^{n-1})$
L
log
L
(

S

n
−
1

)
with vanishing integral. We prove that $T_{\varOmega }$

T
Ω

is bounded on the mixed radial-angular spaces $L_{|x|}^{p}L_{\theta }^{\tilde{p}}( \mathbb{R}^{n})$

L

|
x
|

p

L
θ

p
˜

(

R
n

)
, on the vector-valued mixed radial-angular spaces $L_{|x|}^{p}L_{\theta }^{\tilde{p}}(\mathbb{R}^{n},\ell ^{\tilde{p}})$

L

|
x
|

p

L
θ

p
˜

(

R
n

,

ℓ

p
˜

)
and on the vector-valued function spaces $L^{p}(\mathbb{R}^{n}, \ell ^{\tilde{p}})$

L
p

(

R
n

,

ℓ

p
˜

)
if $1<\tilde{p}\leq p<\tilde{p}n/(n-1)$
1
<

p
˜

≤
p
<

p
˜

n
/
(
n
−
1
)
or $\tilde{p}n/(\tilde{p}+n-1)< p\leq \tilde{p}<\infty $

p
˜

n
/
(

p
˜

+
n
−
1
)
<
p
≤

p
˜

<
∞
. The same conclusions hold for the well-known Riesz transforms and directional Hilbert transforms. It should be pointed out that our proof is based on the Calderón–Zygmund’s rotation method.
Further results on the asymptotic stability of Riemann–Liouville fractional neutral systems with variable delays
Authors: Altun Yener
Published: October 2019

In this paper, the investigation of the asymptotic stability of Riemann–Liouville fractional neutral systems with variable delays has been presented. The advantage of the Lyapunov functional was used to achieve the desired results. The stability criteria obtained for zero solution of the system were formulated as linear matrix inequalities (LMIs) which can be easily solved. The advantage of the considered method is that the integer-order derivatives of the Lyapunov functionals can be directly calculated. Finally, three numerical examples have been evaluated to illustrate that the proposed method is flexible and efficient in terms of computation and to demonstrate the feasibility of established assumptions by MATLAB-Simulink.
Stability analysis of a nonlinear coupled implicit switched singular fractional differential system with p-Laplacian
Authors: Ahmad Manzoor , Zada Akbar , Alzabut Jehad
Published: October 2019

This paper deals with existence, uniqueness, and Hyers–Ulam stability of solutions to a nonlinear coupled implicit switched singular fractional differential system involving Laplace operator$\phi _{p}$ϕp. The proposed problem consists of two kinds of fractional derivatives, that is, Riemann–Liouville fractional derivative of orderβand Caputo fractional derivative of orderσ, where$m-1<\beta $m−1<β,$\sigma < m$σ<m,$m\in \{2,3,\dots \}$m∈{2,3,…}. Prior to proceeding to the main results, the system is converted into an equivalent integral form by the help of Green’s function. Using Schauder’s fixed point theorem and Banach’s contraction principle, the existence and uniqueness of solutions are proved. The main results are demonstrated by an example.
On applications of Caputo k-fractional derivatives
Authors: Farid Ghulam , Latif Naveed , Anwar Matloob , Imran Ali , Ozair Muhammad , Nawaz Madeeha
Published: October 2019

This research explores Caputo k-fractional integral inequalities for functions whose nth order derivatives are absolutely continuous and possess Grüss type variable bounds. Using Chebyshev inequality (Waheed et al. in IEEE Access 7:32137–32145, 2019) for Caputo k-fractional derivatives, several integral inequalities are derived. Further, Laplace transform of Caputo k-fractional derivative is presented and Caputo k-fractional derivative and Riemann–Liouville k-fractional integral of an extended generalized Mittag-Leffler function are calculated. Moreover, using the extended generalized Mittag-Leffler function, Caputo k-fractional differential equations are presented and their solutions are proposed by applying the Laplace transform technique.
The infectious thyroid nodule: A case report of mucormycosis associated with ibrutinib therapy
Authors: Mascarella Marco A. , Schweitzer Lorne , Alreefi Mahmoud , Silver Jennifer , Caglar Derin , Loo Vivian G. , Richardson Keith , Dufresne Philippe , Lee Todd C. , Sadeghi Nader
Published: October 2019

Background

Acute invasive fungal infections of the head and neck secondary to tyrosine kinase inhibitors are rare and potentially life-threatening events.

Case presentation

We report a case of mucormycosis of the thyroid gland in a patient known for chronic lymphocytic leukemia receiving ibrutinib who presented with a rapidly growing thyroid nodule and dysphonia. An acute invasive fungal infection was identified on a core needle biopsy; mucormycosis was confirmed on culture. The patient was successfully treated with surgical debridement and long-term antifungal therapy.

Conclusion

Patients on ibrutinib may be at risk of acute invasive fungal infections of the head and neck.
Combined Micro- and Macro scale X-ray powder diffraction mapping of degraded Orpiment paint in a 17th century still life painting by Martinus Nellius
Authors: Simoen Jonas , De Meyer Steven , Vanmeert Frederik , de Keyser Nouchka , Avranovich Ermanno , Van der Snickt Geert , Van Loon Annelies , Keune Katrien , Janssens Koen
Published: October 2019

The spontaneous chemical alteration of artists’ pigment materials may be caused by several degradation processes. Some of these are well known while others are still in need of more detailed investigation and documentation. These changes often become apparent as color modifications, either caused by a change in the oxidation state in the original material or the formation of degradation products or salts, via simple or more complex, multistep reactions. Arsenic-based pigments such as orpiment (As2S3) or realgar (α-As4S4) are prone to such alterations and are often described as easily oxidizing upon exposure to light. Macroscopic X-ray powder diffraction (MA-XRPD) imaging on a sub area of a still life painting by the 17th century Dutch painter Martinus Nellius was employed in combination with microscopic (μ-) XRPD imaging of a paint cross section taken in the area imaged by MA-XRPD. In this way, the in situ formation of secondary metal arsenate and sulfate species and their migration through the paint layer stack they originate from could be visualized. In the areas originally painted with orpiment, it could be shown that several secondary minerals such as schultenite (PbHAsO4), mimetite (Pb5(AsO4)3Cl), palmierite (K2Pb(SO4)2) and syngenite (K2Ca(SO4)2∙H2O) have formed. Closer inspection of the cross-sectioned paint layer stack with μ-XRPD illustrates that the arsenate minerals schultenite and mimetite have precipitated at the interface between the orpiment layer and the layer below that is rich in lead white, i.e. close to the depth of formation of the arsenate ions. The sulfate palmierite has mostly precipitated at the surface and upper layers of the painting.
Challenges constraining availability and affordability of insulin in Bengaluru region (Karnataka, India): evidence from a mixed-methods study
Authors: Satheesh Gautam , Unnikrishnan M. K. , Sharma Abhishek
Published: October 2019

Introduction

Considering limited global access to affordable insulin, we evaluated insulin access in public and private health sectors in Bengaluru, India.

Methods

Employing modified WHO/HAI methodology, we used mixed-methods analysis to study insulin access and factors influencing insulin supply and demand in Bengaluru in December 2017. We assessed insulin availability, price and affordability in a representative sample of 5 public-sector hospitals, 5 private-sector hospitals and 30 retail pharmacies. We obtained insulin price data from websites of government Jan Aushadhi scheme (JAS) and four online private-sector retail pharmacies. We interviewed wholesalers in April 2018 to understand insulin market dynamics.

Results

Mean availability of insulins on India’s 2015 Essential Medicine List was 66.7% in the public sector, lower than private-sector retail (76.1%) and hospital pharmacies (93.3%). Among private retailers, mean availability was higher among chain (96.7%) than independent pharmacies (68.3%). Non-Indian companies supplied 67.3% products in both sectors. 79.1% products were manufactured in India, of which 60% were marketed by non-Indian companies.

In private retail pharmacies, median consumer prices of human insulin cartridges and pens were 2.5 and 3.6 times, respectively, that of human insulin vials. Analogues depending on delivery device were twice as expensive as human insulin. Human insulin vials were 18.3% less expensive in JAS pharmacies than private retail pharmacies. The lowest paid unskilled worker would pay 1.4 to 9.3 days’ wages for a month’s supply, depending on insulin type and health sector. Wholesaler interviews suggest that challenges constraining patient insulin access include limited market competition, physicians' preference for non-Indian insulins, and the ongoing transition from human to analogue insulin. Rising popularity of online and chain pharmacies may influence insulin access.

Conclusion

Insulin availability in Bengaluru’s public sector falls short of WHO’s 80% target. Insulin remains unaffordable in both private and public sectors. To improve insulin availability and affordability, government should streamline insulin procurement and supply chains at different levels, mandate biosimilar prescribing, educate physicians to pursue evidence-based prescribing, and empower pharmacists with brand substitution. Patients must be encouraged to shop around for lower prices from subsidized schemes like JAS. While non-Indian companies dominate Bengaluru’s insulin market, rising market competition from Indian companies may improve access.
DEGREE OF INTENSITY in English-Chinese translation: a corpus-based approach
Authors: Li Long , Wu Canzhong
Published: October 2019

The claim in translation studies that Chinese tends to have a preference for stronger or more exaggerated terms than does English has not been substantiated by any hard linguistic evidence. One system to approach such perceived differences in intensity is degree of intensity (DOI), which is an important device of fine-tuning taken by a speaker to express interpersonal judgments. However, it has not been systematically studied, in quantitative terms, for the Chinese language, nor has a contrastive study been conducted between English and Chinese. This study aims to adopt a corpus-based approach and investigate the phenomenon, using the Chinese translation of a politically volatile English autobiography by a Chinese migrant writer, Wild Swans (Chang 1991), as the domain of study, and comparing it with another translation of this kind and against two reference corpora of non-translated texts (FLOB and LCMC). The findings of the research suggest that Chinese indeed prefers more and higher degrees of intensity, but they also show that translator’s choice-making plays an important role in the translation of degree of intensity.
CT radiomic features for predicting resectability of oesophageal squamous cell carcinoma as given by feature analysis: a case control study
Authors: Ou Jing , Li Rui , Zeng Rui , Wu Chang-qiang , Chen Yong , Chen Tian-wu , Zhang Xiao-ming , Wu Lan , Jiang Yu , Yang Jian-qiong , Cao Jin-ming , Tang Sun , Tang Meng-jie , Hu Jiani
Published: October 2019

Background

Computed tomography (CT) is commonly used in all stages of oesophageal squamous cell carcinoma (SCC) management. Compared to basic CT features, CT radiomic features can objectively obtain more information about intratumour heterogeneity. Although CT radiomics has been proved useful for predicting treatment response to chemoradiotherapy in oesophageal cancer, the best way to use CT radiomic biomarkers as predictive markers for determining resectability of oesophageal SCC remains to be developed. This study aimed to develop CT radiomic features related to resectability of oesophageal SCC with five predictive models and to determine the most predictive model.

Methods

Five hundred ninety-one patients with oesophageal SCC undergoing contrast-enhanced CT were enrolled in this study, and were composed by 270 resectable cases and 321 unresectable cases. Of the 270 resectable oesophageal SCCs, 91 cases were primary resectable tumours; and the remained 179 cases received neoadjuvant therapy after CT, shrank on therapy, and changed to resectable tumours. Four hundred thirteen oesophageal SCCs including 189 resectable cancers and 224 unresectable cancers were randomly allocated to the training cohort; and 178 oesophageal SCCs including 81 resectable tumours and 97 unresectable tumours were allocated to the validation group. Four hundred ninety-five radiomic features were extracted from CT data for identifying resectability of oesophageal SCC. Useful radiomic features were generated by dimension reduction using least absolute shrinkage and selection operator. The optimal radiomic features were chosen using multivariable logistic regression, random forest, support vector machine, X-Gradient boost and decision tree classifiers. Discriminating performance was assessed with area under receiver operating characteristic curve (AUC), accuracy and F-1score.

Results

Eight radiomic features were selected to create radiomic models related to resectability of oesophageal SCC (P-values < 0.01 for both cohorts). Multivariable logistic regression model showed the best performance (AUC = 0.92 ± 0.04 and 0.87 ± 0.02, accuracy = 0.87 and 0.86, and F-1score = 0.93 and 0.86 in training and validation cohorts, respectively) in comparison with any other model (P-value < 0.001). Good calibration was observed for multivariable logistic regression model.

Conclusion

CT radiomic models could help predict resectability of oesophageal SCC, and multivariable logistic regression model is the most predictive model.
Efficacy of a bystander intervention for preventing dating violence in Brazilian adolescents: short-term evaluation
Authors: dos Santos Karine Brito , Murta Sheila Giardini , do Amaral Vinha Luis Gustavo , de Deus Juliana Silva
Published: October 2019

Peers are the preferred source of help for Brazilian adolescents who experience dating violence. However, they are not always the best informants for effective responses for dealing with situations of violence in romantic relationships among peers. This experimental study aimed to evaluate the short-term efficacy of three aspects of a peer- and bystander approach-based intervention: the intent to offer help, empathy, and bystander attitudes in response to dating violence in a Brazilian sample of adolescents. The study’s participants were 33 adolescents randomized in two groups: experimental group (EG,n = 14) and control group (CG,n = 19). The EG underwent three weekly intervention sessions of 90 min each on the healthy versus violent romantic relationships, the quality of friendship in the peer network, and the role of the bystander, while the CG received no intervention. Evaluations were performed 1 week before and two and half months after the intervention. Statistically significant differences between EG and CG at post-test were not found in intention to help, empathy, and bystander attitudes. Future studies should include evaluations of larger samples and mid- and long-term follow-ups to identify patterns of change over the long term as well as examine barriers to utilization of bystander behaviors by adolescents in Brazilian culture.
Fast and efficient copper-mediated 18F-fluorination of arylstannanes, aryl boronic acids, and aryl boronic esters without azeotropic drying
Authors: Lahdenpohja Salla Orvokki , Rajala Noora Annika , Rajander Johan , Kirjavainen Anna Kaarina
Published: October 2019

Background

Copper-mediated radiofluorination is a straightforward method to produce a variety of [18F]fluoroarenes and [18F]fluoroheteroarenes. To minimize the number of steps in the production of 18F-labelled radiopharmaceuticals, we have developed a short and efficient azeotropic drying-free 18F-labelling method using copper-mediated fluorination. Our goal was to improve the copper-mediated method to achieve wide substrate scope with good radiochemical yields with short synthesis time.

Results

Solid phase extraction with Cu (OTf)2 in dimethylacetamide is a suitable activation method for [18F]fluoride. Elution efficiency with Cu (OTf)2 is up to 79% and radiochemical yield (RCY) of a variety of model molecules in the crude reaction mixture has reached over 90%. Clinically relevant molecules, norepinephrine transporter tracer [18F]NS12137 and monoamine transporter tracer [18F]CFT were produced with 16.5% RCY in 98 min and 5.3% RCY in 64 min, respectively.

Conclusions

Cu (OTf)2 is a suitable elution agent for releasing [18F]fluoride from an anion exchange cartridge. The method is fast and efficient and the Cu-complex is customizable after the release of [18F]fluoride. Alterations in the [18F]fluoride elution techniques did not have a negative effect on the subsequent labelling reactions. We anticipate this improved [18F]fluoride elution technique to supplant the traditional azeotropic drying of [18F]fluoride in the long run and to concurrently enable the variations of the copper-complex.
Translation and validation of the Indian Takayasu clinical activity score (ITAS2010) for the Brazilian Portuguese language
Authors: Fritsch Scheila , Copes Rafaela Martinez , Savioli Bruna , de Aguiar Mariana Freitas , Ciconelli Rozana Mesquita , Azevedo Valderílio Feijó , de Souza Alexandre W. S.
Published: October 2019

Background

The Indian Takayasu Clinical Activity Score (ITAS2010) was developed in 2010 as an assessment tool for disease activity in patients with Takayasu arteritis (TA). It has since been widely used in different studies and in clinical practice for the management of patients with TA. The present study aims to translate the ITAS2010 into Brazilian Portuguese language and to validate it for use in clinical practice in Brazil.

Methods

For this cross-sectional study, the ITAS2010 was translated in accordance with the guidelines described by Beaton et al. and then applied with 27 patients with TA on three assessments by two rheumatologists working independently. To measure interrater agreement, the assessments were performed on the same day within approximately 1 hour. One of the rheumatologists performed a second evaluation of patients with TA within 7 to 14 days to measure intrarater agreement.

Results

The correlation coefficient for the ITAS2010 score between the two raters was high (r = 0.916; p < 0.0001), as well as the intraclass correlation coefficient (ICC) [0.918 with a 95% confidence interval (95CI): 0.828–0.962]. The correlation coefficient and the ICC for intrarater agreement were moderate for ITAS2010 (r = 0.633; p < 0.0001 and ICC = 0.594; 95CI: 0.292–0.790). The ITAS2010 at baseline was compared with the physician’s global assessment (PGA) and with Kerr’s criteria for detecting disease activity in TA. Higher ITAS2010 scores were observed in patients with active and grumbling/persistent disease than in those presenting inactive disease according to the PGA [1.5 (0.0–3.0) vs. 0.0 (0.0–0.0); p = 0.0025]. Patients with active disease according to the Kerr’s criteria had also higher ITAS2010 scores than those considered in remission [3.0 (3.0–7.0) vs. 0.0 (0.0–0.0); p = 0.0068].

Conclusions

The Brazilian Portuguese version of the ITAS2010 is a valid and reproducible tool for the assessment of disease activity in TA and it is an additional tool for the routine evaluation of Brazilian patients with TA.