bluuebunny/crossref_metadata_2025 huggingface dataset:
Complement C3 overexpression activates JAK2/STAT3 pathway and correlates with gastric cancer progression
Authors: Yuan Kaitao , Ye Jinning , Liu Zhenguo , Ren Yufeng , He Weiling , Xu Jianbo , He Yulong , Yuan Yujie
Published: January 2020

Background

Localized C3 deposition is a well-known factor of inflammation. However, its role in oncoprogression of gastric cancer (GC) remains obscured. This study aims to explore the prognostic value of C3 deposition and to elucidate the mechanism of C3-related oncoprogression for GC.

Methods

From August to December 2013, 106 GC patients were prospectively included. The regional expression of C3 and other effectors in gastric tissues were detected by WB, IHC, qRT-PCR and other tests. The correlation of localized C3 deposition and oncologic outcomes was determined by 5-year survival significance. Human GC and normal epithelial cell lines were employed to detect a relationship between C3 and STAT3 signaling pathway in vitro experiments.

Results

C3 and C3a expression were markedly enhanced in GC tissues at both mRNA and protein levels compared with those in paired nontumorous tissues. According to IHC C3 score, 65 (61.3%) and 41 (38.7%) patients had high and low C3 deposition, respectively. C3 deposition was negatively correlated with plasma levels of C3 and C3a (both P < 0.001) and positively correlated with pathological T and TNM stages (both P < 0.001). High C3 deposition was identified as an independent prognostic factor of poor 5-year overall survival (P = 0.045). In vitro C3 administration remarkably enhanced p-JAK2/p-STAT3 expression in GC cell lines but caused a reduction of such activation when pre-incubated with a C3 blocker. Importantly, C3 failed to activate such signaling in cells pre-treated with a JAK2 inhibitor.

Conclusions

Localized C3 deposition in the tumor microenvironment is a relevant immune signature for predicting prognosis of GC. It may aberrantly activate JAK2/STAT3 pathway allowing oncoprogression.

Trial registration

ClinicalTrials.gov, NCT02425930, Registered 1st August 2013.
Ulcer metastasis? Anatomical locations of recurrence for patients in diabetic foot remission
Authors: Petersen Brian J. , Rothenberg Gary M. , Lakhani Priti J. , Zhou Min , Linders David R. , Bloom Jonathan D. , Wood Katherine A. , Armstrong David G.
Published: January 2020

Background

The “cancer analogy” is powerful for communicating risk to and organizing care for patients with diabetic foot syndrome. One potentially underappreciated similarity between cancer and foot ulcers is that both can recur at anatomical locations distinct from the primary occurrence, albeit with different physiological mechanisms. Few studies have characterized the location of diabetic foot ulcer recurrence, and these have been limited by considering only the first recurrent wound following a recent‐healed wound. We therefore characterized the anatomical locations at which diabetic foot ulcers are likely to recur considering multiple wounds during follow‐up and the locations of all prior wounds documented in the participant's history.

Methods

We completed a secondary analysis of existing data from a 129 participant multi‐center study of participants in diabetic foot remission. The primary outcome was plantar foot ulceration, and each participant was followed for 34 weeks or until withdrawing consent, allowing characterization of all wounds occurring. We stratified the anatomical locations of wounds prior to the trial by the following outcome categories during the trial: no recurrence, recurrence to the same anatomical location, recurrence to a different anatomical location on the same foot, and recurrence to the contralateral foot.

Results

A large percentage (48%) of wounds recurred to the contralateral foot, and the proportion of subsequent foot ulcer to the contralateral limb was largely unaffected by the anatomical location of foot ulcer prior to the study. Only 17% of prior diabetic foot ulcers were followed by recurrence to the same anatomical location. Rates of recurrence remained high during treatment of a wound (0.41 foot ulcer/ulcer‐year). Participants had documented wounds to 2.2 distinct anatomical locations on average, and more than 60% of participants had wounds to more than one plantar location by the end of the study.

Conclusions

Given the significant morbidity, mortality, and resource utilization associated with foot ulcer recidivism, quality and evidenced‐based preventive care is essential. Our results better characterize the burden of recurrence and to what anatomy recurrence is most likely. These insights may benefit providers and patients alike for the provision of high‐quality preventive care thereby resulting in reduced morbidity, mortality, and cost.

Trial registration

The study providing the data for this secondary analysis was registered on ClinicalTrials.gov (NCT02647346) on January 6, 2016. The study was retrospectively registered.
A double-blind placebo-controlled trial of azithromycin to reduce mortality and improve growth in high-risk young children with non-bloody diarrhoea in low resource settings: the Antibiotics for Children with Diarrhoea (ABCD) trial protocol
Authors:   The ABCD study team
Published: January 2020

Background

Acute diarrhoea is a common cause of illness and death among children in low- to middle-income settings. World Health Organization guidelines for the clinical management of acute watery diarrhoea in children focus on oral rehydration, supplemental zinc and feeding advice. Routine use of antibiotics is not recommended except when diarrhoea is bloody or cholera is suspected. Young children who are undernourished or have a dehydrating diarrhoea are more susceptible to death at 90 days after onset of diarrhoea. Given the mortality risk associated with diarrhoea in children with malnutrition or dehydrating diarrhoea, expanding the use of antibiotics for this subset of children could be an important intervention to reduce diarrhoea-associated mortality and morbidity. We designed the Antibiotics for Childhood Diarrhoea (ABCD) trial to test this intervention.

Methods

ABCD is a double-blind, randomised trial recruiting 11,500 children aged 2–23 months presenting with acute non-bloody diarrhoea who are dehydrated and/or undernourished (i.e. have a high risk for mortality). Enrolled children in Bangladesh, India, Kenya, Malawi, Mali, Pakistan and Tanzania are randomised (1:1) to oral azithromycin 10 mg/kg or placebo once daily for 3 days and followed-up for 180 days. Primary efficacy endpoints are all-cause mortality during the 180 days post-enrolment and change in linear growth 90 days post-enrolment.

Discussion

Expanding the treatment of acute watery diarrhoea in high-risk children to include an antibiotic may offer an opportunity to reduce deaths. These benefits may result from direct antimicrobial effects on pathogens or other incompletely understood mechanisms including improved nutrition, alterations in immune responsiveness or improved enteric function. The expansion of indications for antibiotic use raises concerns about the emergence of antimicrobial resistance both within treated children and the communities in which they live. ABCD will monitor antimicrobial resistance. The ABCD trial has important policy implications. If the trial shows significant benefits of azithromycin use, this may provide evidence to support reconsideration of antibiotic indications in the present World Health Organization diarrhoea management guidelines. Conversely, if there is no evidence of benefit, these results will support the current avoidance of antibiotics except in dysentery or cholera, thereby avoiding inappropriate use of antibiotics and reaffirming the current guidelines.

Trial registration

Clinicaltrials.gov, NCT03130114. Registered on April 26 2017.
Study protocol for a randomized controlled trial on the effect of the Diabetic Foot Guidance System (SOPeD) for the prevention and treatment of foot musculoskeletal dysfunctions in people with diabetic neuropathy: the FOotCAre (FOCA) trial I
Authors: Ferreira J. S. S. P. , Cruvinel Junior R. H. , Silva E. Q. , Veríssimo J. L. , Monteiro R. L. , Pereira D. S. , Suda E. Y. , Sartor C. D. , Sacco I. C. N.
Published: January 2020

Background

This study is part of a series of two clinical trials. Taking into account the various musculoskeletal alterations of the foot and ankle in people with diabetic peripheral neuropathy (DPN) and the need for self-care to avoid more serious dysfunctions and complications, a self-manageable exercise protocol that focuses on strengthening the foot muscles is presented as a potentially effective preventive method for foot and gait complications. The aim of this trial is to investigate the effect of a customized rehabilitation technology, the Diabetic Foot Guidance System (SOPeD), on DPN status, functional outcomes and gait biomechanics in people with DPN.

Methods/design

Footcare (FOCA) trial I is a randomized, controlled and parallel two-arm trial with blind assessment. A total of 62 patients with DPN will be allocated into either a control group (recommended foot care by international consensus with no foot exercises) or an intervention group (who will perform exercises through SOPeD at home three times a week for 12 weeks). The exercise program will be customized throughout its course by a perceived effort scale reported by the participant after completion of each exercise. The participants will be assessed at three different times (baseline, completion at 12 weeks, and follow-up at 24 weeks) for all outcomes. The primary outcomes will be DPN symptoms and severity classification. The secondary outcomes will be foot–ankle kinematics and kinetic and plantar pressure distribution during gait, tactile and vibration sensitivities, foot health and functionality, foot strength, and functional balance.

Discussion

As there is no evidence about the efficacy of rehabilitation technology in reducing DPN symptoms and severity or improving biomechanical, clinical, and functional outcomes for people with DPN, this research can contribute substantially to clarifying the therapeutic merits of software interventions. We hope that the use of our application for people with DPN complications will reduce or attenuate the deficits caused by DPN. This rehabilitation technology is freely available, and we intend to introduce it into the public health system in Brazil after demonstrating its effectiveness.

Trial registration

ClinicalTrials.gov,NCT04011267. Registered on 8 July 2019.
Correction to: An individualised versus a conventional pneumoperitoneum pressure strategy during colorectal laparoscopic surgery: rationale and study protocol for a multicentre randomised clinical study
Authors:   and for the IPPCollapse-II study group, Diaz-Cambronero O. , Mazzinari G. , Errando C. L. , Schultz M. J. , Lorente B. Flor , García-Gregorio N. , Montañés M. Vila , Robles-Hernández Daniel , Arnal L. E. Olmedilla , Martín-De-Pablos A. , Marí A. Marqués , Navarro M. P. Argente
Published: January 2020

After publication of our article [1] the authors have notified us that there are changes in the primary outcome and the statistical analysis plan of the study.
Yeast-encapsulated essential oils: a new perspective as an environmentally friendly larvicide
Authors: Workman Michael J. , Gomes Bruno , Weng Ju-Lin , Ista Linnea K. , Jesus Camila P. , David Mariana R. , Ramalho-Ortigao Marcelo , Genta Fernando A. , Matthews Scott K. , Durvasula Ravi , Hurwitz Ivy
Published: January 2020

Background

Effective mosquito control approaches incorporate both adult and larval stages. For the latter, physical, biological, and chemical control have been used with varying results. Successful control of larvae has been demonstrated using larvicides including insect growth regulators, e.g. the organophosphate temephos, as well as various entomopathogenic microbial species. However, a variety of health and environmental issues are associated with some of these. Laboratory trials of essential oils (EO) have established the larvicidal activity of these substances, but there are currently no commercially available EO-based larvicides. Here we report on the development of a new approach to mosquito larval control using a novel, yeast-based delivery system for EO.

Methods

Food-grade orange oil (OO) was encapsulated into yeast cells following an established protocol. To prevent environmental contamination, a proprietary washing strategy was developed to remove excess EO that is adsorbed to the cell exterior during the encapsulation process. The OO-loaded yeast particles were then characterized for OO loading, and tested for efficacy against Aedes aegypti larvae.

Results

The composition of encapsulated OO extracted from the yeast microparticles was demonstrated not to differ from that of un-encapsulated EO when analyzed by high performance liquid chromatography. After lyophilization, the oil in the larvicide comprised 26–30 percentage weight (wt%), and is consistent with the 60–65% reduction in weight observed after the drying process. Quantitative bioassays carried with Liverpool and Rockefeller Ae. aegypti strains in three different laboratories presented LD50 of 5.1 (95% CI: 4.6–5.6) to 27.6 (95% CI: 26.4–28.8) mg/l, for L1 and L3/L4 mosquito larvae, respectively. LD90 ranged between 18.9 (95% CI: 16.4–21.7) mg/l (L1 larvae) to 76.7 (95% CI: 69.7–84.3) mg/l (L3/L4 larvae).

Conclusions

The larvicide based on OO encapsulated in yeast was shown to be highly active (LD50 < 50 mg/l) against all larval stages of Ae. aegypti. These results demonstrate its potential for incorporation in an integrated approach to larval source management of Ae. aegypti. This novel approach can enable development of affordable control strategies that may have significant impact on global health.
Cutaneous and mucocutaneous leishmaniasis: experience of a Mediterranean hospital
Authors: Garrido-Jareño Marta , Sahuquillo-Torralba Antonio , Chouman-Arcas Rabab , Castro-Hernández Iván , Molina-Moreno José Miguel , Llavador-Ros Margarita , Gómez-Ruiz María Dolores , López-Hontangas José Luis , Botella-Estrada Rafael , Salavert-Lleti Miguel , Pemán-García Javier
Published: January 2020

Background

Leishmaniasis, considered by the World Health Organization as one of the most important tropical diseases, is endemic in the Mediterranean Basin. The aim of this study was to evaluate epidemiological and clinical characteristics of cutaneous (CL) and mucocutaneous leishmaniasis (MCL) in La Fe University Hospital, Valencia, Spain. The particular focus was on diagnosis techniques and clinical differences according to the immunological status of the patients.

Methods

An eleven-year retrospective observational study of CL and MCL episodes at the hospital was performed. Epidemiological, clinical and therapeutic variables of each case, together with the microbiological and anatomopathological diagnosis, were analyzed.

Results

A total of 42 patients were included, 30 of them were male and 28 were immunocompetent. Most of the cases (36/42) were diagnosed in the last 5 years (2013–2017). The incidence of CL and MCL increased from 3.6/100,000 (2006–2012) to 13.58/100,000 (2013–2017). The majority of the patients (37/42) exhibited CL, in 30 cases as single lesions (30/37). Ulcerative lesions were more common in immunosuppressed patients (13/14) than in immunocompetent patients (20/28), (P = 0.2302). The length of lesion presence before diagnosis was 7.36 ± 6.72 months in immunocompetent patients and 8.79 ± 6.9 months in immunosuppressed patients (P = 0.1863). Leishmania DNA detection (92.3%) was the most sensitive diagnostic technique followed by Giemsa stain (65%) and histopathological examination (53.8%). Twelve patients (12/42) had close contact with dogs or were living near to kennels, and 10 of them did not present underlying conditions. Intralesional glucantime (21/42) and liposomal amphotericin B (7/42) were the most common treatments administered in monotherapy. All patients evolved successfully and no relapse was reported.

Conclusions

Some interesting clinical and epidemiological differences were found in our series between immunocompetent and immunosuppressed patients. Future studies can take these results further especially by studying patients with biological therapy. Skin biopsies combining NAAT with histological techniques are the most productive techniques for CL or MCL diagnosis.
Cardiometabolic risk factors correlated with the incidence of dysglycaemia in a Brazilian normoglycaemic sample: the Baependi Heart Study cohort
Authors: De Oliveira Camila Maciel , Tureck Luciane Viater , Alvares Danilo , Liu Chunyu , Horimoto Andrea Roseli Vançan Russo , de Oliveira Alvim Rafael , Krieger José Eduardo , Pereira Alexandre C.
Published: January 2020

Background

Dysglycaemia is defined by elevated glucose levels in the blood, commonly characterized by impaired fasting glucose, impaired glucose tolerance, elevated glycated haemoglobin, or diabetes mellitus (DM) diagnosis. The abnormal levels of glucose may occur many years before DM, a condition known as prediabetes, which is correlated with comorbidities such as cardiovascular diseases. Therefore, the aim of this study was to investigate the incidence of prediabetic dysglycaemia and its relationship with cardiometabolic risk factors at a 5-year follow-up, based on an initially normoglycaemic sample in the Baependi Heart Study cohort.

Methods

The data used comes from the Baependi Heart Study cohort, which consists of two periods: cycle 1 (2005–2006) and cycle 2 (2010–2013). For this study, we excluded those who had fasting blood glucose ≥ 100 mg/dL or were taking anti-diabetic medications at baseline, and those that had diabetes diagnosed in cycle 2. Mixed-effects logistic regression models were used to assess the association between cardiometabolic risk factors and the incidence of dysglycaemia, including a familiar random effect such as a cluster.

Results

The incidence of prediabetic dysglycaemia was 12.8%, and it did not differ between men and women (14.4% and 11.6%, respectively). Two models were analysed to investigate the relationship between cardiometabolic risk factors and the occurrence of prediabetic dysglycaemia. The model that better explained the occurrence of dysglycaemia over the 5 years, after correction, included the waist circumference (WC) (measures and Δ), systolic blood pressure (SBP), HDL-c levels, and age. Although sex was not associated with the incidence of dysglycaemia, women and men showed differences in cardiometabolic risk factors related to glucose impairment: men who developed dysglycaemia showed, in parallel, higher LDL-c levels, TC/HDL-c ratio and DBP measurements; while these parameters remained similar between women who developed dysglycaemia and dysglycaemia-free women, after 5 years.

Conclusions

In an initially normoglycaemic sample of a highly mixed population living in a traditional Brazilian lifestyle, important cardiometabolic risk factors were associated with the occurrence of prediabetic dysglycaemia, and this relationship appeared to be more important in men. These results provide important insights about cardiovascular risk in prediabetic individuals.
Mesenchymal stem cells alleviate liver injury induced by chronic-binge ethanol feeding in mice via release of TSG6 and suppression of STAT3 activation
Authors: Wan Yue-Meng , Li Zhi-qiang , Zhou Qiong , Liu Chang , Wang Men-Jie , Wu Hui-Xin , Mu Yun-Zhen , He Yue-Feng , Zhang Yuan , Wu Xi-Nan , Li Yu-Hua , Xu Zhi-Yuan , Wu Hua-Mei , Xu Ying , Yang Jin-Hui , Wang Xiao-Fang
Published: January 2020

Background

Mesenchymal stem cells (MSCs) are a population of pluripotent cells that might be used for treatment of liver disease. However, the efficacy of MSCs for mice with alcoholic hepatitis (AH) and its underlying mechanism remains unclear.

Methods

MSCs were isolated from the bone marrow (BM) of 4–6-week-old male C57BL/6 N mice. AH was induced in female mice by chronic-binge ethanol feeding for 10 days. The mice were given intraperitoneal injections of MSCs with or without transfection or AG490, recombinant mouse tumor necrosis factor (TNF)-α-stimulated gene/protein 6 (rmTSG-6), or saline at day 10. Blood samples and hepatic tissues were collected at day 11. Various assays such as biochemistry, histology, and flow cytometry were performed.

Results

MSCs reduced AH in mice, decreasing liver/body weight ratio, liver injury, blood and hepatic lipids, malondialdehyde, interleukin (IL)-6, and TNF-ɑ, but increasing glutathione, IL-10, and TSG-6, compared to control mice. Few MSCs engrafted into the inflamed liver. Knockdown of TSG-6 in MSCs significantly attenuated their effects, and injection of rmTSG-6 achieved similar effects to MSCs. The signal transducer and activator of transcription 3 (STAT3) was activated in mice with AH, and MSCs and rmTSG-6 inhibited the STAT3 activation. Injection of MSCs plus AG490 obtained more alleviation of liver injury than MSCs alone.

Conclusions

BM-MSCs injected into mice with AH do not engraft the liver, but they secrete TSG-6 to reduce liver injury and to inhibit STAT3 activation.
Surfactant protein D (SP-D) gene polymorphism rs721917 is an independent predictor of acute kidney injury development in sepsis patients: a prospective cohort study
Authors: Liu Jiao , Yao Jianying , Zhang Lidi , Chen Yizhu , Du Hangxiang , Wen Zhenliang , Chen Dechang
Published: January 2020

Background

Currently, there are no reliable predictors of risk of development and severity of acute kidney injury (AKI) in septic patients. The surfactant protein D (SP-D) polymorphism rs721917C/T is associated with a greater susceptibility to AKI in the Chinese population. Our aim was to evaluate the value of SP-D polymorphisms rs721917C/T and of plasma SP-D levels to predict the risk of development of AKI (defined with KDIGO criterion) in septic patients.

Methods

The study enrolled septic patients admitted to the Critical Care Department of two tertiary care hospitals. SP-D rs721917C/T polymorphisms were determined using the PCR-SSP method. Plasma SP-D and urine NGAL contents were measured using commercially available ELISA kits.

Results

330 septic patients were included. Their SOFA scores were 12 ± 3. Patients with AKI (n = 156) had higher plasma SP-D levels (median: 153 ng/mL, range 111–198 ng/mL) and urinary NGAL levels (median: 575 ng/mL, range 423–727 ng/mL) than those without AKI (SP-D median: 124 ng/mL, range 81–159 ng/mL, P = 0.001; NGAL median: 484 ng/mL, range 429–573 ng/mL). Plasma SP-D levels of AKI patients were correlated with urinary NGAL contents (r = 0.853). In 32 patients receiving continuous renal replacement therapy (CRRT), plasma SP-D levels correlated with duration of CRRT (r = 0.448). The area under the receiver operating characteristic curve for plasma SP-D levels to predict AKI was 0.84. Patients with AKI had a higher rate of rs721917 CC genotype (AKI: 35% vs. non-AKI: 20%; P = 0.012), but a significantly lower rate of TT genotype (AKI: 19% vs. non-AKI: 26%; P = 0.005). SP-D rs721917 CC genotype was an independent predictor of AKI (P = 0.044) and mortality (P = 0.014).

Conclusion

Our study showed that increased plasma SP-D level is associated with a higher risk of AKI in patients with sepsis. The SP-D rs721917CC genotype is an independent and significant predictor of AKI development and mortality of septic patients. The SP-D rs721917C/T polymorphisms should be further studied as diagnostic and prognostic biomarkers to facilitate early recognition of AKI.
Accuracy of ventilator-associated events for the diagnosis of ventilator-associated lower respiratory tract infections
Authors: Pouly Olivier , Lecailtel Sylvain , Six Sophie , Préau Sébastien , Wallet Frédéric , Nseir Saad , Rouzé Anahita
Published: January 2020

Background

The aim of this study was to investigate the concordance between ventilator-associated events (VAE) and ventilator-associated lower respiratory tract infections (VA-LRTI), and their impact on outcome.

Methods

This retrospective study was performed in five 10-bed ICUs of a teaching hospital, during a 2-year period. Ventilator-associated lower respiratory tract infections (VA-LRTI), including ventilator-associated tracheobronchitis (VAT) and ventilator-associated pneumonia (VAP) were prospectively diagnosed. The agreement between VAE, VAT and VAP was assessed by k statistics.

Results

A total of 1059 patients (15,029 ventilator-days) were included. 268 VAP (17.8 per 1000 ventilator-days), 127 VAT (8.5 per 1000 ventilator-days) and 262 VAE (17.4 per 1000 ventilator-days) were diagnosed. There was no agreement between VAT and VAE, and the agreement was poor between VAP and VAE (k = 0.12, 95% CI 0.03–0.20). VAE and VA-LRTI were associated with significantly longer duration of mechanical ventilation, ICU and hospital length of stay. VAP, VAT and VAE were not significantly associated with mortality in multivariate analysis.

Conclusions

The agreement was poor between VAE and VAP. No agreement was found between VAE and VAT. VAE episodes were significantly associated with longer duration of mechanical ventilation and length of stay, but not with ICU mortality.
Cache-aided mobile edge computing for B5G wireless communication networks
Authors: Xia Junjuan , Li Chao , Lai Xiazhi , Lai Shiwei , Zhu Fusheng , Deng Dan , Fan Liseng
Published: January 2020

This paper investigates a cache-aided mobile edge computing (MEC) network, where the source offloads the computation task to multiple destinations with computation capacity, with the help of a cache-aided relay. For the proposed cache-aided MEC networks, two destination selection criteria have been proposed to maximize the computation capacity of the selected destination, the channel gain of relay link and the channel gain of direct link, respectively. Similarly, three destination selection criteria have been proposed for the cache-free MEC networks based on the computation capacities of destinations and the channel gains of transmission links, respectively. To evaluate the system performance regarding the latency constraint, we provide the outage probability for the proposed network which is defined based on the transmission-plus-computation time. Our analysis suggests that caching can significantly alleviate the impact of increasing the size of computation task, since only half of the transmission time of cache-free network is required. However, the cache-aided network can not fully exploit the signal from both direct and relay links, thus the improvement by caching is less significant in the high signal-to-noise ratio (SNR) region, compared with the cache-free network employing the destination with maximal channel gain of direct link. Numerical results are given to validate our analysis.
Full-duplex decode-and-forward relaying with joint relay-antenna selection
Authors: Gilan Mahsa Shirzadian , Nguyen Ha H.
Published: January 2020

This paper is concerned with wireless relay networks that employ K full-duplex (FD) decode-and-forward relays to help a source to communicate with a destination. Each FD relay is equipped with multiple antennas, some for receiving and some for transmitting. The paper considers joint relay-antenna selection schemes that are based on the instantaneous channel conditions for two cases of antenna configurations, namely fixed antenna configuration (FAC) and adaptive antenna configuration (AAC). Under FAC, the transmit and receive antennas at each relay are fixed, whereas in the case of AAC an antenna at a relay can be configured to be either a transmit or a receive antenna.In addition to equal power allocation between the source and selected relay, a power scaling approach to counteract the effect of residual self-interference is also examined. Closed-form expressions of the outage probability and average capacity are obtained and provide important insights on the system performance. The accuracy of the obtained expressions are corroborated by simulation results. In particular, it is shown that under FAC and without power scaling, the diversity order approaches K as the self-interference (SI) level gets smaller, while it approaches zero whenever the SI level is nonzero and the SNR increases without bound. Under FAC and with power scaling, the diversity order approaches K for any SI level. For the case of AAC and without power scaling, the diversity order approaches 2K for small SI level. When power scaling is applied in AAC, the diversity order approaches 2K at any SI level.
On Cauchy–Schwarz inequality for N-tuple diamond-alpha integral
Authors: Hu Xi-Mei , Tian Jing-Feng , Chu Yu-Ming , Lu Yan-Xia
Published: January 2020

In this paper, we present some new Cauchy–Schwarz inequalities for N-tuple diamond-alpha integral on time scales. The obtained results improve and generalize some Cauchy–Schwarz type inequalities given by many authors.
An enhanced stability criterion for linear time-delayed systems via new Lyapunov–Krasovskii functionals
Authors: Duan Wenyong , Li Yan , Chen Jian
Published: January 2020

The stability problem of linear systems with time-varying delays is studied by improving a Lyapunov–Krasovskii functional (LKF). Based on the newly developed LKF, a less conservative stability criterion than some previous ones is derived. Firstly, to avoid introducing the terms with $h^{2}(t)$h2(t), which are not convenient to directly use the convexity of linear matrix inequality (LMI), the type of integral terms $\{\int _{s}^{t}\dot{x}(u)\,du, \int _{t-h}^{s}\dot{x}(u)\,du\}${∫stx˙(u)du,∫t−hsx˙(u)du} is used in the LKF instead of $\{\int _{s}^{t}x(u)\,du, \int _{t-h}^{s}x(u)\,du\}${∫stx(u)du,∫t−hsx(u)du}. Secondly, two couples of integral terms $\{\int _{s}^{t}\dot{x}(u)\,du, \int _{t-h(t)}^{s}\dot{x}(u)\,du\}${∫stx˙(u)du,∫t−h(t)sx˙(u)du}, and $\{\int _{s}^{t-h(t)}\dot{x}(u)\,du, \int _{t-h}^{s}\dot{x}(u)\,du\}${∫st−h(t)x˙(u)du,∫t−hsx˙(u)du} are supplemented in the integral functionals $\int _{t-h(t)}^{t}\dot{x}(u)\,du$∫t−h(t)tx˙(u)du and $\int _{t-h}^{t-h(t)}\dot{x}(u)\,du$∫t−ht−h(t)x˙(u)du, respectively, so that the time delay, its derivative, and information between them can be fully utilized. Thirdly, the LKF is further augmented by two delay-dependent non-integral items. Finally, three numerical examples are presented under two different delay sets, to show the effectiveness of the proposed approach.
RANKL/RANK promotes the migration of gastric cancer cells by interacting with EGFR
Authors: Wan Xing , Song Yongxi , Fang Honghong , Xu Ling , Che Xiaofang , Wang Shuo , Zhang Xiaomeng , Zhang Lingyun , Li Ce , Fan Yibo , Hou Kezuo , Li Zhi , Wang Xueqing , Liu Yunpeng , Qu Xiujuan
Published: January 2020

Background

The incidence and mortality rates of gastric cancer (GC) rank in top five among all malignant tumors. Chemokines and their receptor‐signaling pathways reportedly play key roles in the metastasis of malignant tumor cells. Receptor activator of nuclear factor κB ligand (RANKL) is a member of the tumor necrosis factor family, with strong chemokine‐like effects. Some studies have pointed out that the RANKL/RANK pathway is vital for the metastasis of cancer cells, but the specific mechanisms in GC remain poorly understood.

Results

This study reports original findings in cell culture models and in patients with GC. Flow cytometry and western blotting analyses showed that RANK was expressed in BGC‐823 and SGC‐7901 cells in particular. Chemotaxis experiments and wound healing assay suggested that RANKL spurred the migration of GC cells. This effect was offset by osteoprotegerin (OPG), a decoy receptor for RANKL. RANKL contributed to the activation of human epidermal growth factor receptor (HER) family pathways. The lipid raft core protein, caveolin 1 (Cav‐1), interacted with both RANK and human epidermal growth factor receptor‐1(EGFR). Knockdown of Cav‐1 blocked the activation of EGFR and cell migration induced by RANKL. Moreover, RANK‐positive GC patients who displayed higher levels of EGFR expression had poor overall survival.

Conclusions

In summary, we confirmed that with the promotion of RANKL, RANK and EGFR can form complexes with the lipid raft core protein Cav‐1, which together promote GC cell migration. The formation of the RANK‐Cav‐1‐EGFR complex provides a novel mechanism for the metastasis of GC. These observations warrant confirmation in independent studies, in vitro and in vivo. They also inform future drug target discovery research and innovation in the treatment of GC progression.
Re-analysis of whole blastocysts after trophectoderm biopsy indicated chromosome aneuploidy
Authors: Ou Zhanhui , Chen Zhiheng , Yin Minna , Deng Yu , Liang Yunhao , Wang Wenjun , Yao Yuanqing , Sun Ling
Published: January 2020

Background

To compare the concordance between trophectoderm (TE) analysis and whole blastocyst analysis of embryos from chromosomal structural rearrangement (SR) carriers.

Method

Sixty-three abnormal blastocysts identified by preimplantation genetic testing for chromosomal structural rearrangement (PGT-SR) were included. The whole blastocysts were processed through multiple displacement amplification cycle and sequenced for 24-chromosome aneuploidy screening by next-generation sequencing (NGS). The sequencing results were compared with those of TE biopsy from the same blastocysts and the primary chromosomal rearrangement of the couples.

Results

Analysis of the 63 blastocysts showed 68% (43/63) complete concordance between TE sequencing analysis and whole blastocyst results. Approximately one third (20/63, 32%) of the sequencing results showed some level of discordance between the two samples. Of these, 14% (9/63) of the embryos were identified as euploid after whole blastocyst sequencing. Among them, seven blastocysts were classified as chromosome mosaicism (five whole chromosomes, two segmental) after TE analysis, while two displayed non-SR related segmental changes in the TE biopsy. Of the original analyses, 70% (44/63) of findings were associated with the primary parental chromosomal rearrangement, while 30% (19/63) had no association.

Conclusions

TE biopsy with NGS for PGT-SR is an efficient strategy to identify embryos suitable for transfer. While there was a high concordance between TE and whole blastocyst chromosome results, some embryos classified as mosaic in the original analysis and therefore unsuitable for transfer were reclassified as chromosomally balanced. To maximize the number of embryos available for PGT-SR patients, we suggest that embryos with mosaic non-SR chromosomal rearrangement should be stored and considered for transfer after appropriate counseling.
Researching social innovation: is the tail wagging the dog?
Authors: Rhule Emma L. M. , Allotey Pascale A.
Published: January 2020

Background

Social Innovation in health initiatives have the potential to address unmet community health needs. For sustainable change to occur, we need to understand how and why a given intervention is effective. Bringing together communities, innovators, researchers, and policy makers is a powerful way to address this knowledge gap but differing priorities and epistemological backgrounds can make collaboration challenging.

Main text

To overcome these barriers, stakeholders will need to design policies and work in ways that provide an enabling environment for innovative products and services. Inherently about people, the incorporation of community engagement approaches is necessary for both the development of social innovations and accompanying research methodologies. Whilst the 'appropriate' level of participation is linked to intended outcomes, researchers have a role to play in better understanding how to harness the power of community engagement and to ensure that community perspectives form part of the evidence base that informs policy and practice.

Conclusions

To effectively operate at the intersection between policy, social innovation, and research, all collaborators need to enter the process with the mindset of learners, rather than experts. Methods – quantitative and qualitative – must be selected according to research questions. The fields of implementation research, community-based participatory research, and realist research, amongst others, have much to offer. So do other sectors, notably education and business. In all this, researchers must assume the mantel of responsibility for research and not transfer the onus to communities under the guise of participation. By leveraging the expertise and knowledge of different ecosystem actors, we can design responsive health systems that integrate innovative approaches in ways that are greater than the sum of their parts.
The effect of transactional analysis on the self-esteem of imprisoned women: a clinical trial
Authors: Torkaman Mahya , Farokhzadian Jamileh , Miri Sakineh , Pouraboli Batool
Published: January 2020

Background

The imprisoned women usually have low self-esteem and suffer from various physical and mental complaints; they may suffer from feelings of emptiness, isolation, and depression. Transactional analysis (TA) is part of a comprehensive system attributed to the individual and social psychiatry for personal development of self-esteem among the imprisoned women. Therefore, the present study aimed to investigate the effect of TA group-training on the self-esteem of imprisoned women.

Methods

This clinical trial was conducted among the imprisoned women in a prison in Southeastern Iran using pretest-posttest design. In this regard, 76 women were randomly allocated to the intervention (n = 35) and control (n = 41) groups. The TA group-training program was held for eight 90-min sessions for the intervention group. Data were collected using a demographic questionnaire and the Rosenberg’s self-esteem scale (RSES). Later, all participants were evaluated before and 1 month after the intervention.

Results

In pre-test, the mean scores of self-esteem were 11.8 ± 4.67 and 7.97 ± 4.52 for the intervention and control groups, respectively. These scores showed low levels of self-esteem and the difference between the two groups was significant (p = 0.001, t = − 3.61). In the post-test, the mean scores of self-esteem improved to the moderate level (22 ± 2.52) in the intervention group compared to the control group (8.92 ± 4.04). This indicates the significant improvement of self-esteem in the intervention group (p = 0.001, t = 17.15).

Conclusions

The results showed that TA group-training had a significant effect on self-esteem. Therefore, the experienced and expert counselors and psychologists are recommended to hold transactional analysis group-training courses to enhance self-esteem among women prisoners.

Trial registration

Iranian Registry of Clinical Trials, IRCT20170725035289N5 Date registered: 25/08/2018.
The effect of antithrombin added to recombinant human-soluble thrombomodulin for severe community-acquired pneumonia-associated disseminated intravascular coagulation: a retrospective cohort study using a nationwide inpatient database
Authors: Suzuki Jun , Sasabuchi Yusuke , Hatakeyama Shuji , Matsui Hiroki , Sasahara Teppei , Morisawa Yuji , Yamada Toshiyuki , Yasunaga Hideo
Published: January 2020

Background

Studies showed potential benefits of recombinant human-soluble thrombomodulin (rhTM) and antithrombin for treating sepsis associated disseminated intravascular coagulation. However, benefits of their combination have been inconclusive.

Methods

Using a nationwide inpatient database in Japan, we performed propensity-score matched analyses to compare outcomes between rhTM combined with antithrombin and rhTM alone for severe community-acquired pneumonia associated disseminated intravascular coagulation from July 2010 to March 2015. The outcomes included in-hospital mortality and requirement of red cell transfusion.

Results

Propensity score matching created 189 pairs of patients who received rhTM combined with antithrombin or rhTM alone within 2 days of admission. There was no significant difference between the two groups for in-hospital mortality (40.2% vs. 45.5%). Patients treated with rhTM and antithrombin were more likely to require red cell transfusion than those treated with rhTM alone (37.0% vs. 25.9%).

Conclusions

Compared with rhTM alone, combination of rhTM with antithrombin for severe community-acquired pneumonia-associated disseminated intravascular coagulation may be ineffective for reducing mortality and may increase bleeding.
Development and validation of a nomogram based on CT images and 3D texture analysis for preoperative prediction of the malignant potential in gastrointestinal stromal tumors
Authors: Ren Caiyue , Wang Shengping , Zhang Shengjian
Published: January 2020

Background

Gastrointestinal stromal tumors (GISTs), which are the most common mesenchymal tumors of the digestive system, are treated varyingly according to the malignancy. The purpose of this study is to develop and validate a nomogram for preoperative prediction of the malignant potential in patients with GIST.

Methods

A total of 440 patients with pathologically confirmed GIST after surgery in our hospital from January 2011 to July 2019 were retrospectively analyzed. They were randomly divided into the training set (n = 308) and validation set (n = 132). CT signs and texture features of each patient were analyzed and predictive model were developed using the least absolute shrinkage and selection operator (lasso) regression. Then a nomogram based on selected parameters was developed. The predictive effectiveness of nomogram was evaluated by the area under receiver operating characteristic (ROC) curve (AUC). Concordance index (C-index) and calibration plots were formulated to evaluate the reliability and accuracy of the nomogram by bootstrapping based on internal (training set) and external (validation set) validity. The clinical application value of the nomogram was determined through the decision curve analysis (DCA).

Results

Totally 156 GIST patients with low-malignant (very low and low risk) and 284 ones with high-malignant potential (intermediate and high risk) are enrolled in this study. The prediction nomogram consisting of size, cystoid variation and meanValue had an excellent discrimination both in training and validation sets (AUCs (95% confidence interval(CI)): 0.935 (0.908, 0.961), 0.933 (0.892, 0.974); C-indices (95% CI): 0.941 (0.912, 0.956), 0.935 (0.901, 0.982); sensitivity: 81.4, 90.6%; specificity: 75.0, 75.7%; accuracy: 88.0, 88.6%, respectively). The calibration curves indicated a good consistency between the actual observation and nomogram prediction for differentiating GIST malignancy. Decision curve analysis demonstrated that the nomogram was clinically useful.

Conclusion

This study presents a prediction nomogram that incorporates the CT signs and texture parameter, which can be conveniently used to facilitate the preoperative individualized prediction of malignancy in GIST patients.
Quantification of tumor burden in multiple myeloma by atlas-based semi-automatic segmentation of WB-DWI
Authors: Almeida Sílvia D. , Santinha João , Oliveira Francisco P. M. , Ip Joana , Lisitskaya Maria , Lourenço João , Uysal Aycan , Matos Celso , João Cristina , Papanikolaou Nikolaos
Published: January 2020

Background

Whole-body diffusion weighted imaging (WB-DWI) has proven value to detect multiple myeloma (MM) lesions. However, the large volume of imaging data and the presence of numerous lesions makes the reading process challenging. The aim of the current study was to develop a semi-automatic lesion segmentation algorithm for WB-DWI images in MM patients and to evaluate this smart-algorithm (SA) performance by comparing it to the manual segmentations performed by radiologists.

Methods

An atlas-based segmentation was developed to remove the high-signal intensity normal tissues on WB-DWI and to restrict the lesion area to the skeleton. Then, an outlier threshold-based segmentation was applied to WB-DWI images, and the segmented area’s signal intensity was compared to the average signal intensity of a low-fat muscle on T1-weighted images. This method was validated in 22 whole-body DWI images of patients diagnosed with MM. Dice similarity coefficient (DSC), sensitivity and positive predictive value (PPV) were computed to evaluate the SA performance against the gold standard (GS) and to compare with the radiologists. A non-parametric Wilcoxon test was also performed. Apparent diffusion coefficient (ADC) histogram metrics and lesion volume were extracted for the GS segmentation and for the correctly identified lesions by SA and their correlation was assessed.

Results

The mean inter-radiologists DSC was 0.323 ± 0.268. The SA vs GS achieved a DSC of 0.274 ± 0.227, sensitivity of 0.764 ± 0.276 and PPV 0.217 ± 0.207. Its distribution was not significantly different from the mean DSC of inter-radiologist segmentation (p = 0.108, Wilcoxon test). ADC and lesion volume intraclass correlation coefficient (ICC) of the GS and of the correctly identified lesions by the SA was 0.996 for the median and 0.894 for the lesion volume (p < 0.001). The duration of the lesion volume segmentation by the SA was, on average, 10.22 ± 0.86 min, per patient.

Conclusions

The SA provides equally reproducible segmentation results when compared to the manual segmentation of radiologists. Thus, the proposed method offers robust and efficient segmentation of MM lesions on WB-DWI. This method may aid accurate assessment of tumor burden and therefore provide insights to treatment response assessment.
Use of argatroban in combination with nafamostat mesilate in open-heart surgery for a pediatric patient with heparin-induced thrombocytopenia type II: a case report
Authors: Kawamoto Shuji , Kusudo Eriko , Fukuda Kazuhiko
Published: January 2020

Background

Heparin-induced thrombocytopenia type II (HIT II) is a rare, immune-mediated complication of heparin therapy and can cause life-threatening thromboembolism. However, perioperative anticoagulation therapy for patients with a complication of HIT II has not been established.

Case presentation

A 6-year-old boy with tetralogy of Fallot underwent radical intracardiac repair with administration of argatroban at 1 year old due to positive HIT antibody. Reoperation was scheduled for pulmonary valve insufficiency, using argatroban and nafamostat mesilate as anticoagulants. Argatroban has a long onset time and the activated coagulation time (ACT) requires 7–26 h to return to the preadministration level, making hemorrhage control difficult, while half-life of nafamostat mesilate is shorter than that of argatroban. Celite ACT reflects the effects of both argatroban and nafamostat mesilate, but kaolin ACT reflects only the effect of argatroban. Due to the early termination of argatroban administration based on Celite and kaolin ACTs, ACT recovered to ≤ 200 s at 5 h after the end of argatroban administration.

Conclusion

Celite and kaolin ACTs can be used as markers to obtain close control of the required dose of argatroban in combination with nafamostat mesilate for the management of HIT II patients.
Toward the realization of cardiac regenerative medicine using pluripotent stem cells
Authors: Kishino Yoshikazu , Fujita Jun , Tohyama Shugo , Okada Marina , Tanosaki Sho , Someya Shota , Fukuda Keiichi
Published: January 2020

Heart transplantation (HT) is the only radical treatment available for patients with end-stage heart failure that is refractory to optimal medical treatment and device therapies. However, HT as a therapeutic option is limited by marked donor shortage. To overcome this difficulty, regenerative medicine using human-induced pluripotent stem cells (hiPSCs) has drawn increasing attention as an alternative to HT.

Several issues including the preparation of clinical-grade hiPSCs, methods for large-scale culture and production of hiPSCs and cardiomyocytes, prevention of tumorigenesis secondary to contamination of undifferentiated stem cells and non-cardiomyocytes, and establishment of an effective transplantation strategy need to be addressed to fulfill this unmet medical need. The ongoing rapid technological advances in hiPSC research have been directed toward the clinical application of this technology, and currently, most issues have been satisfactorily addressed. Cell therapy using hiPSC-derived cardiomyocytes is expected to serve as an integral component of realistic medicine in the near future and is being potentially viewed as a treatment that would revolutionize the management of patients with severe heart failure.