bluuebunny/crossref_metadata_2025 huggingface dataset:
Impaired Condensin Complex and Aurora B kinase underlie mitotic and chromosomal defects in hyperdiploid B-cell ALL
Authors: Molina Oscar , Vinyoles Meritxell , Granada Isabel , Roca-Ho Heleia , Gutierrez-Agüera Francisco , Valledor Luis , López-López Carlos Manuel , Rodríguez-González Pablo , Trincado Juan Luis , Tirados-Menéndez Sofía , Pal Deepali , Ballerini Paola , Den Boer Monique L. , Plensa Isabel , Perez-Iribarne Maria del Mar , Rodriguez-Perales Sandra , Calasanz Maria JOSE , Ramírez Manuel , Rodríguez Rene , Camos Mireia , Calvo Maria , Bueno Clara , Menendez Pablo
Published: April 2020

B-cell acute lymphoblastic leukemia (B-ALL) is the most common pediatric cancer, and high-hyperdiploidy (HyperD) identifies the most common subtype of pediatric B-ALL. Despite HyperD is an initiating oncogenic event affiliated to childhood B-ALL, the mitotic and chromosomal defects associated to HyperD B-ALL (HyperD-ALL) remain poorly characterized. Here, we have used 54 primary pediatric B-ALL samples to characterize the cellular-molecular mechanisms underlying the mitotic/chromosome defects predicated to be early pathogenic contributors in HyperD-ALL. We report that HyperD-ALL blasts are low proliferative and show a delay in early mitosis at prometaphase, associated to chromosome alignment defects at the metaphase plate leading to robust chromosome segregation defects and non-modal karyotypes. Mechanistically, biochemical, functional and mass-spectrometry assays revealed that condensin complex is impaired in HyperD-ALL cells, leading to chromosome hypocondensation, loss of centromere stiffness and mis-localization of the chromosome passenger complex proteins Aurora B Kinase (AURKB) and Survivin in early mitosis. HyperD-ALL cells show chromatid cohesion defects and impaired spindle assembly checkpoint (SAC) thus undergoing mitotic slippage due to defective AURKB and impaired SAC activity, downstream of condensin complex defects. Chromosome structure/condensation defects and hyperdiploidy were reproduced in healthy CD34+ stem/progenitor cells upon inhibition of AURKB and/or SAC. Collectively, hyperdiploid B-ALL is associated to defective condensin complex, AURKB and SAC.
Resistive Random Access Memory (RRAM): an Overview of Materials, Switching Mechanism, Performance, Multilevel Cell (mlc) Storage, Modeling, and Applications
Authors: Zahoor Furqan , Azni Zulkifli Tun Zainal , Khanday Farooq Ahmad
Published: April 2020

In this manuscript, recent progress in the area of resistive random access memory (RRAM) technology which is considered one of the most standout emerging memory technologies owing to its high speed, low cost, enhanced storage density, potential applications in various fields, and excellent scalability is comprehensively reviewed. First, a brief overview of the field of emerging memory technologies is provided. The material properties, resistance switching mechanism, and electrical characteristics of RRAM are discussed. Also, various issues such as endurance, retention, uniformity, and the effect of operating temperature and random telegraph noise (RTN) are elaborated. A discussion on multilevel cell (MLC) storage capability of RRAM, which is attractive for achieving increased storage density and low cost is presented. Different operation schemes to achieve reliable MLC operation along with their physical mechanisms have been provided. In addition, an elaborate description of switching methodologies and current voltage relationships for various popular RRAM models is covered in this work. The prospective applications of RRAM to various fields such as security, neuromorphic computing, and non-volatile logic systems are addressed briefly. The present review article concludes with the discussion on the challenges and future prospects of the RRAM.
Interactions between sucrose and jasmonate signalling in the response to cold stress
Authors: Wingler Astrid , Tijero Verónica , Müller Maren , Yuan Benqi , Munné-Bosch Sergi
Published: April 2020

Background

Jasmonates play an important role in plant stress and defence responses and are also involved in the regulation of anthocyanin synthesis in response to sucrose availability. Here we explore the signalling interactions between sucrose and jasmonates in response to cold stress in Arabidopsis.

Results

Sucrose and cold treatments increased anthocyanin content additively. Comprehensive profiling of phytohormone contents demonstrated that jasmonates, salicylic acid and abscisic acid contents increased in response to sucrose treatment in plants grown on agar, but remained considerably lower than in plants grown in compost. The gibberellin GA3 accumulated in response to sucrose treatment but only at warm temperature. The role of jasmonate signalling was explored using the jasmonate response mutants jar1–1 and coi1–16. While the jar1–1 mutant lacked jasmonate-isoleucine and jasmonate-leucine, it accumulated 12-oxo-phytodienoic acid at low temperature on agar medium. Altered patterns of abscisic acid accumulation and higher sugar contents were found in the coi1–16 mutant when grown in compost. Both mutants were able to accumulate anthocyanin and to cold acclimate, but the jar-1-1 mutant showed a larger initial drop in whole-rosette photosystem II efficiency upon transfer to low temperature.

Conclusions

Hormone contents are determined by interactions between temperature and sucrose supply. Some of these effects may be caused indirectly through senescence initiation in response to sucrose availability. During cold stress, the adjustments of hormone contents may compensate for impaired jasmonate signalling, enabling cold acclimation and anthocyanin accumulation in Arabidopsis jasmonate response mutants, e.g. through antagonistic interactions between gibberellin and jasmonate signalling.
GPR30 receptor promotes preoperative anxiety-induced postoperative hyperalgesia by up-regulating GABAA-α4β1δ subunits in periaqueductal gray in female rats
Authors: Jiang Ming , Sun Yu’e , Lei Yishan , Hu Fan , Xia Zhengrong , Liu Yue , Ma Zhengliang , Gu Xiaoping
Published: April 2020

Background

G-protein coupled estrogen receptor 30 (GPR30) was proved the specific estrogen receptor relating to mechanical hyperalgesia. Studies have shown that the GABAA receptor subunits α4, β1, and δ in the periaqueductal gray (PAG) neurons promote the descending facilitation system. This study inquired into whether and how GPR30 and GABAA-α4β1δ in the PAG promote preoperative anxiety-induced postoperative hyperalgesia in female rats.

Methods

All the female rats were subjected to the single prolonged stress (SPS) to stimulate preoperative anxiety. Subsequently, mechanical allodynia was evaluated before and after the incision, based on the paw withdrawal mechanical threshold (PWMT). The selective GPR30 agonist G1 and antagonist G15 were locally microinjected into the PAG. The expression of GPR30, protein kinase A (PKA), and GABAA receptor subunits α4, β1, and δ in the PAG neurons were detected using western blotting and immunofluorescence.

Results

Behavioral testing revealed that Group S and Group I decreased the nociceptive threshold levels of PWMT in female rats. PWMT in Group S + I decreased more than that of Group S and Group I. Further, results of western blotting showed the expression of GPR30, PKA, and GABAA α4, β1, and δ subunits significantly up-regulated in Group S + I, and immunofluorescence indicated that the neurons of PAG in Group S + I appeared simultaneously immunopositive for GPR30 and GABAA α4, β1, and δ receptors. After microinjection of G1 into the PAG, female rats with plantar incision continued to exhibit significant hyperalgesia until postoperative 48 h. On the other hand, microinjection of G15 with SPS and plantar incision procedure relieved postoperative hyperalgesia in female rats. Western blotting demonstrated that intra-PAG injection of G15 markedly decreased the GPR30, PKA, and GABAA α4, β1, and δ levels in Group G15 + I.

Conclusions

Our results indicate that the GPR30-PKA-GABAAα4β1δ pathway in the PAG promotes preoperative anxiety-induced postoperative hyperalgesia in female rats. This mechanism might be a potential novel therapeutic target for hyperalgesia in females.
Anomalous right coronary artery with interarterial course depicting an unusual case of an electrical storm: a case presentation
Authors: Pradhan Snehasis , Gresa Kciku , Trappe Hans-Joachim
Published: April 2020

Background

The condition of anomalous aortic origin of the right coronary artery (AAORCA) with an interarterial course leads to few, if any, clinical problems. Malignant presentation of the often non-significant AAORCA associated with conduction system abnormalities is a rare finding. Surgical repair, even for highly symptomatic patients, is still controversial. However, in this case, the surgery brought a paradigm shift in treatment modality, improving the symptoms of this patient.

Case presentation

We report a case of a 52-year-old man with severe chest pain and recurrent electrical storms with an implanted cardiac resynchronization therapy defibrillator (CRT-D) device. Coronary angiography and computed tomography (CT) revealed the rare anomalous aortic origin of the right coronary artery (AAORCA) with a high interarterial course between the aorta and the pulmonary trunk. As symptoms typically develop on exertion, placing the patient at an increased risk of ischemic distress, a stress myocardial perfusion imaging study helped to identify his high-risk status. Although patient-specific, a surgical repair was the only concrete step agreed upon after multiple collaborative discussions with the cardiac surgeons. Surgery significantly improved the symptoms, with the patient reporting resolution of his chest pain, as well as no documented inappropriate defibrillator activity on follow-up appointments.

Conclusion

One purpose of reporting the case study was to underscore the risk factors associated with AAORCA, challenging claims of its benign nature. This case complements existing findings demonstrating that ischemic distress consequent to the right coronary artery (RCA) compression may precede the rare incidence of an electrical storm. Importantly, the case-study emphasizes the significance of integrated multimodality imaging in clinical practice as well as providing real-world evidence for the efficacy of surgical repair in highly symptomatic patients with AAORCA with an interarterial course.
Relationships of accelerometer-based measured objective physical activity and sedentary behaviour with cognitive function: a comparative cross-sectional study of China’s elderly population
Authors: Wu Zhi-jian , Wang Zhu-ying , Hu Bing-qian , Zhang Xu-hui , Zhang Fan , Wang Hou-lei , Li Fang-hui
Published: April 2020

Background

This study explored the effects of physical activity and sedentary behaviour on the decline of cognitive ability among the elderly. To compensate for the limitations of self-reported physical activity, objective measures were used.

Methods

A cross-sectional survey of 308 aged people mean 68.66 ± 5.377 years, in Nanjing, China, was conducted. Physical activity was measured using the ActiGraph GT3X+, and cognitive function was measured using the Montreal Cognitive Assessment.

Results

The overall participant model, adjusted for age, BMI, education, and monthly average income, found that light physical activity (β = 0.006, p < 0.01), moderate-vigorous physical activity (β = 0.068, p < 0.001), and total physical activity (β = 0.006, p < 0.01) had a significant linear relationship with cognitive ability, while sedentary time did not (β = − 0.020, p>0.05). Further, light physical activity only affects the cognitive ability of elderly females (β = 0.006, p < 0.05). There was an inverted ‘U’ association between moderate-vigorous physical activity and cognitive ability. The association models found that moderate-vigorous physical activity in the 22.13 min·day− 1~38.79 min·day− 1 range affected cognitive ability most beneficially, with the highest beta coefficient among all groups (β = 0.091, p < 0.05).

Conclusions

While physical activity can significantly improve cognitive ability among the elderly, sedentary behaviour is associated with decreased cognitive function across genders.
Long-term care use after a stroke or femoral fracture and the role of family caregivers
Authors: van der Burg Doutsen A. , Diepstraten Maaike , Wouterse Bram
Published: April 2020

Background

There has been a shift from institutional care towards home care, and from formal to informal care to contain long-term care (LTC) costs in many countries. However, substitution to home care or informal care might be harder to achieve for some conditions than for others. Therefore, insight is needed in differences in LTC use, and the role of potential informal care givers, across specific conditions. We analyze differences in LTC use of previously independent older patients after a fracture of femur and stroke, and in particular examine to what extent having a partner and children affects LTC use for these conditions.

Methods

Using administrative data on Dutch previously independent older people (55+) with a fracture of femur or stroke in 2013, we investigate their LTC use in the year after the condition takes place. We use administrative treatment data to select individuals who were treated by a medical specialist for a stroke or femoral fracture in 2013. Subsequent LTC use is measured as using no formal care, home care, institutional care or being deceased at 13 consecutive four-weekly periods after initial treatment. We relate long-term care use to having a partner, having children, other personal characteristics and the living environment.

Results

The probability to use no formal care 1 year after the initial treatment is equally high for both conditions, but patients with a fracture are more likely to use home care, while patients with a stroke are more likely to use institutional care or have died. Having a spouse has a negative effect on home care and institutional care use, but the timing of the effect, especially for institutional care, differs strongly between the two conditions. Having children also has a negative effect on formal care use, and this effect is consistently larger for patients with a fracture than patients with a stroke.

Conclusion

As the condition and the effect of potential informal care givers matter for subsequent long-term care use, policy makers should take the expected prevalence of specific conditions within the older people population into account when designing long-term care policies.
Feasibility and acceptability of commonly used screening instruments to identify frailty among community-dwelling older people: a mixed methods study
Authors: Ambagtsheer Rachel C. , Archibald Mandy M. , Lawless Michael , Kitson Alison , Beilby Justin
Published: April 2020

Background

Frailty exposes older people to an elevated risk of a range of negative outcomes. Emerging evidence that frailty can be effectively treated within community settings has stimulated calls for more proactive screening within primary care. Assessing feasibility is a critical preliminary step in assessing the efficacy of interventions such as screening. However, few studies have explored the feasibility and acceptability of administering frailty screening instruments within general practice, and even fewer have incorporated patient perspectives. Our study had three objectives: To 1) assess overall feasibility of the instruments (completion time and rate); 2) assess patient acceptability towards the instruments; and 3) assess the feasibility and acceptability of the instruments to administering nurses.

Methods

The feasibility and acceptability of several frailty screening instruments (PRISMA-7, Edmonton Frail Scale, FRAIL Scale Questionnaire, Gait Speed, Groningen Frailty Indicator, Reported Edmonton Frail Scale and Kihon Checklist) was explored within the context of a larger diagnostic test accuracy (DTA) study. Completion time and rate was collected for all participants (N = 243). A sub-sample of patients (n = 30) rated each instrument for ease of completion and provided comment on perceived acceptability. Lastly, five of six administering nurses involved in the DTA study participated in semi-structured face-to-face interviews, rating the instruments against several feasibility and acceptability criteria (time, space, equipment, skill required to implement, acceptability to patients and nurses, ease of scoring) and providing comment on their responses.

Results

The PRISMA-7 returned the highest overall feasibility and acceptability, requiring minimal space, equipment, skills and time to implement, and returning the fastest completion rate and highest patient and nurse acceptability rating. All screening instruments were faster to implement than the two reference standards (Fried’s Frailty Phenotype and Frailty Index). Self-administered instruments were subject to lower rates of completion than nurse-administered instruments.

Conclusions

This study has demonstrated that a number of commonly used frailty screening instruments are potentially feasible for implementation within general practice. Ultimately, more research is needed to determine how contextual factors, such as differences in individual patient and clinician preferences, setting and system factors, impact on the feasibility of screening in practice.
Statistical methods for predicting tuberculosis incidence based on data from Guangxi, China
Authors: Zheng Yanling , Zhang Liping , Wang Lei , Rifhat Ramziya
Published: April 2020

Background

Tuberculosis (TB) remains a serious public health problem with substantial financial burden in China. The incidence of TB in Guangxi province is much higher than that in the national level, however, there is no predictive study of TB in recent years in Guangxi, therefore, it is urgent to construct a model to predict the incidence of TB, which could provide help for the prevention and control of TB.

Methods

Box-Jenkins model methods have been successfully applied to predict the incidence of infectious disease. In this study, based on the analysis of TB incidence in Guangxi from January 2012 to June 2019, we constructed TB prediction model by Box-Jenkins methods, and used root mean square error (RMSE), mean absolute error (MAE) and mean absolute percentage error (MAPE) to test the performance and prediction accuracy of model.

Results

From January 2012 to June 2019, a total of 587,344 cases of TB were reported and 879 cases died in Guangxi. Based on TB incidence from January 2012 to December 2018, the SARIMA((2),0,(2))(0,1,0)12 model was established, the AIC and SC of this model were 2.87 and 2.98, the fitting accuracy indexes, such as RMSE, MAE and MAPE were 0.98, 0.77 and 5.8 respectively; the prediction accuracy indexes, such as RMSE, MAE and MAPE were 0.62, 0.45 and 3.77, respectively. Based on the SARIMA((2),0,(2))(0,1,0)12 model, we predicted the TB incidence in Guangxi from July 2019 to December 2020.

Conclusions

This study filled the gap in the prediction of TB incidence in Guangxi in recent years. The established SARIMA((2),0,(2))(0,1,0)12 model has high prediction accuracy and good prediction performance. The results suggested the change trend of TB incidence predicted by SARIMA((2),0,(2))(0,1,0)12 model from July 2019 to December 2020 was similar to that in the previous two years, and TB incidence will experience slight decrease, the predicted results can provide scientific reference for the prevention and control of TB in Guangxi, China.
Prevalence, antimicrobial susceptibility patterns, serotypes and risk factors for group B streptococcus rectovaginal isolates among pregnant women at Kenyatta National Hospital, Kenya; a cross-sectional study
Authors: Jisuvei Salano Clayton , Osoti Alfred , Njeri Maina Anne
Published: April 2020

Background

Estimates of Group B Streptococcus (GBS) disease burden, antimicrobial susceptibility, and serotypes in pregnant women are limited for many resource-limited countries including Kenya. These data are required to inform recommendations for prophylaxis and treatment of infections due to GBS.

Methods

We evaluated the prevalence, antimicrobial susceptibility patterns, serotypes, and risk factors associated with rectovaginal GBS colonization among pregnant women receiving antenatal care at Kenyatta National Hospital (KNH) between August and November 2017. Consenting pregnant women between 12 and 40 weeks of gestation were enrolled. Interview-administered questionnaires were used to assess risk factors associated with GBS colonization. An anorectal swab and a lower vaginal swab were collected and cultured on Granada agar for GBS isolation. Positive colonies were tested for antimicrobial susceptibility to penicillin G, ampicillin, vancomycin, and clindamycin using the disk diffusion method. Serotyping was performed by latex agglutination. Logistic regression was used to identify factors associated with GBS colonization.

Results

A total of 292 women were enrolled. Median age was 30 years (Interquartile range {IQR} 26–35) and a median gestational age of 35 weeks (IQR 30–37). Overall GBS was identified in 60/292 (20.5%) of participants. Among the positive isolates, resistance was detected for penicillin G in 42/58 (72.4%) isolates, ampicillin in 32/58 (55.2%) isolates, clindamycin in 14/46 (30.4%) isolates, and vancomycin in 14/58 (24.1%) isolates. All ten GBS serotypes were isolated, and 37/53 (69.8%) of GBS positive participants were colonized by more than one serotype. None of the risk factors was associated with GBS colonization.

Conclusion

The prevalence of GBS colonization was high among antenatal women at KNH. In addition, a high proportion of GBS isolates were resistant to commonly prescribed intrapartum antibiotics. Hence, other measures like GBS vaccination is a potentially useful approaches to GBS prevention and control in this population. Screening of pregnant mothers for GBS colonization should be introduced and antimicrobial susceptibility test performed on GBS positive samples to guide antibiotic prophylaxis.
"RETRACTED ARTICLE:Successful implementation of an enhanced
recovery after surgery (ERAS) protocol reduces nausea and vomiting after infratentorial
craniotomy for tumour resection: a randomized controlled trial
Authors: Lu Dan , Wang Yuan , Zhao Tianzhi , Liu Bolin , Ye Lin , Zhao Lanfu , Zhao Binfang , Li Mingjuan , Ma Lin , Li Zhengmin , Niu Jiangtao , Lv Wenhai , Zhang Yufu , Zheng Tao , Xue Yafei , Chen Lei , Chen Long , Sun Xude , Gao Guodong , Chen Bo , He Shiming
Published: April 2020

Background

Infratentorial craniotomy patients have a high incidence of
postoperative nausea and vomiting (PONV). Enhanced Recovery After Surgery (ERAS)
protocols have been shown in multiple surgical disciplines to improve outcomes,
including reduced PONV. However, very few studies have described the application
of ERAS to infratentorial craniotomy. The aim of this study was to examine
whether our ERAS protocol for infratentorial craniotomy could improve
PONV.

Methods

We implemented an evidence-based, multimodal ERAS protocol for
patients undergoing infratentorial craniotomy. A total of 105 patients who
underwent infratentorial craniotomy were randomized into either the ERAS group
(n = 50) or the control group (n = 55). Primary outcomes were the incidence of
vomiting, nausea score, and use of rescue antiemetic during the first 72 h after
surgery. Secondary outcomes included postoperative anxiety level, sleep quality,
and complications.

Results

Over the entire 72 h post-craniotomy observation period, the
cumulative incidence of vomiting was significantly lower in the ERAS group than
in the control group. Meanwhile, the incidence of vomiting was significantly
lower in the ERAS group on postoperative days (PODs) 2 and 3. Notably, the
proportion of patients with mild nausea (VAS 0–4) was higher in the ERAS group
as compared to the control group on PODs 2 or 3. Additionally, the postoperative
anxiety level and quality of sleep were significantly better in the ERAS
group.

Conclusion

Successful implementation of our ERAS protocol in infratentorial
craniotomy patients could attenuate postoperative anxiety, improve sleep
quality, and reduce the incidence of PONV, without increasing the rate of
postoperative complications.

Trial registration

ChiCTR-INR-16009662, 27 Oct 2016, Clinical study on the development and efficacy
evaluation of Enhanced Recovery After Surgery (ERAS) in Neurosurgery.
Leg massage during pregnancy with unrecognized deep vein thrombosis could be life threatening: a case report
Authors: Sutham Krongkarn , Na-Nan Sukumpat , Paiboonsithiwong Salilthip , Chaksuwat Pakorn , Tongsong Theera
Published: April 2020

Background

Traditional massage seems to be safe but not entirely risk free, though serious adverse events are very rare. This report is aimed at illustrating a rare but fatal presentation of massive pulmonary embolism caused by leg massage and also to encourage both massage providers and pregnant women to be aware of undetected or subtle deep vein thrombosis, which could be a life threatening condition as a consequence of leg massage.

Case presentation

A 25-year-old primigravid Thai woman underwent massage at a traditional massage shop at 25th week of gestation. Shortly after leg and foot massage, she had a sudden onset of dyspnea, followed by consciousness alteration, brief spastic-like convulsion, became unconscious and suffered a cardiac arrest. Basic life support (BLS) at the event scene as well as during transfer and advanced cardiovascular life support (ACLS) at the hospital were provided, resulting in successful resuscitation but persistent coma. Bedside echocardiography showed poor contractility of the dilated right ventricle, and pulmonary embolism was suspected. CT angiography (CTA) revealed multiple concentric intraluminal filling defects within the right and left pulmonary arteries, indicating massive pulmonary embolism. The fetus died in utero and spontaneous labor and vaginal delivery occurred.

Conclusion

Leg massage in patients with deep vein thrombosis can dislodge thrombi, leading to life threatening pulmonary embolism, and should be contraindicated. Since pregnant women are at a higher risk of undetected or subtle thromboembolism, traditional massage in pregnant women should be contraindicated unless they are proven to have no such risk.
Clinicopathological and prognostic value of SNHG6 in cancers: a systematic review and a meta-analysis
Authors: Zhang Shuo , Qiu Dandan , Xie Xiaohong , Shen Yong
Published: April 2020

Background

Dysregulation of the long non-coding RNA small nucleolar RNA host gene 16 (lncRNA SNHG6) has been found in multiple cancers. However, a definite conclusion on the clinical value of lncRNA SNHG6 expression in human cancers has not been determined. The purpose of the present meta-analysis was to comprehensively elucidate the association between SNHG6 expression and clinical outcomes in cancers.

Methods

A systematic search was performed through the PubMed, Web of Science, Chinese National Knowledge Infrastructure (CNKI), and Wangfang databases for relevant studies. The pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were collected to estimate the prognostic value, and the odds ratios (ORs) with 95% CIs were used to evaluate the relationship between lncRNA SNHG6 expression and clinicopathological features, including tumor invasion depth, lymph node metastasis (LNM), distance metastasis (DM), and TNM stage.

Results

In total, 914 patients from 13 studies were included in this meta-analysis. The pooled results suggested that evaluated SNHG6 expression could predict an unfavorable overall survival (OS) (HR = 2.04, 95% CI:1.56–2.52) with no heterogeneity (I2 = 0.0%, p = 0.996). Subgroup analysis indicated a significant association between high SNHG6 expression and shorter OS in those studies with digestive system cancers (HR = 2.05, 95% CI: 1.47–2.62), or with sample size < 70 (HR = 2.70, 95% CI: 1.29–4.11), or with multivariate analysis (HR = 2.04, 95% CI: 1.44–2.64). Moreover, elevated SNHG6 expression was positively associated with tumor invasion depth (OR = 1.76, 95% CI: 1.18–2.63), LNM (OR = 1.60, 95% CI: 1.18–2.17), DM (OR = 1.90, 95% CI: 1.37–2.64) and advanced TNM stage (OR = 1.88, 95% CI: 1.36–2.60) in patients with cancers.

Conclusions

High lncRNA SNHG6 expression was correlated with tumor invasion depth, LNM, DM, and advanced TNM stage, suggesting that SNHG6 may serve as a promising prognostic biomarker of human cancers.
Cytology cell blocks from malignant pleural effusion are good candidates for PD-L1 detection in advanced NSCLC compared with matched histology samples
Authors: Zou Yinying , Xu Liming , Tang Qiusu , You Qihan , Wang Xiaoling , Ding Wei , Zhao Jing , Ren Guoping
Published: April 2020

Background

Detection of programmed cell death ligand-1 (PD-L1) by immunohistochemistry (IHC) has been commonly used to predict the efficacy of treatment with PD-1/PD-L1 inhibitors. However, there is limited literature regarding the reliability of PD-L1 testing using malignant pleural effusion (MPE) cell blocks. Here, we assess PD-L1 expression in sections from MPE cell blocks and evaluate the value of IHC double staining in the interpretation of PD-L1 expression.

Methods

In all, 124 paired formalin-fixed tissues from advanced NSCLC patients, including MPE cell blocks and matched histology samples, were included. PD-L1 expression was assessed using the SP263 assay, and the tumor proportion score (TPS) and the staining intensity were evaluated. PD-L1 staining results were also compared between IHC double and single staining techniques.

Results

PD-L1 expression was concordant in most paired cases (86/101, 85.1%) among three TPS cut-offs (<1%, 1–49% and ≥ 50%), with a kappa value of 0.774. Moreover, a significant difference in PD-L1 expression between MPE cell blocks and biopsy samples was observed (p = 0.005). For the 15 discordant pairs, 13 MPE cell block samples showed increased expression of PD-L1. Compared with the standard IHC single PD-L1 assay, double staining with anti-TTF-1 and anti-PD-L1 revealed a negative effect on PD-L1 expression testing and resulted in weaker staining intensity and a lower TPS (p = 0.000).

Conclusions

MPE cell block samples are good candidates for PD-L1 expression detection in advanced NSCLC patients. The mechanism and clinical significance of the higher PD-L1 expression rate in MPE cell blocks compared with small biopsy samples remain to be evaluated prospectively.
Catastrophic health expenditure: a comparative study between hypertensive patients with and without complication in rural Shandong, China
Authors: Zhang Xinyi , Xu Qiongqiong , Guo Xiaolei , Jing Zhengyue , Sun Long , Li Jiajia , Zhou Chengchao
Published: April 2020

Background

Some previous studies have assessed catastrophic health expenditure (CHE) in households with hypertensive patients, but few have examined the difference of CHE in hypertensive patients with and without complications. The purpose of this study is to compare the incidence and determinants of CHE between hypertensive patients with and without complications.

Methods

Data of this study were from a cross-sectional study in Shandong Province in China in 2016. Of the recruited 3457 hypertensive patients registered in the NCDs management system in the sampling villages, 3113 completed the survey, with a response rate of 90.05%.CHE was defined as out-of-pocket payments for hypertensive care that equaled or exceeded 40% of the household capacity to pay (non-food expenditure). Hypertension complications (e.g., stroke, coronary heart disease, hypertensive kidney disease, etc.) were collected in this study, which was categorized into 0 (no), 1(single), and 2 and more according to the types of hypertensive complications. We employed Chi-square test to explore associated factors and logistic regression model to identify the determinants of CHE.

Results

The incidence of CHE and impoverishment is 13.6 and 10.8% among hypertensive patients. The incidence of CHE with one complication is 25.3% (Ρ = 0.000, OR = 2.29) and 47.3% (P = 0.000, OR = 3.60) in patients with two or more complications, which are both statistically higher than that in patients without complication (6.1%). Across all types of patients, income levels are inversely related to the incidence of CHE. Patients who use outpatient or inpatient service are more likely to experience CHE (Ρ = 0.000). Factors including living arrangements, family size, educational attainment are found to be significantly associated with CHE in some subgroups (Ρ <0.05).

Conclusions

CHE and impoverishment incidence among hypertensive patients are both high in rural China. Patients with hypertensive complication are at higher catastrophic risk than those without complication. More attention needs to be paid to households with hypertension patients, especially for those with hypertension complications.
Characterizing relaxin receptor expression and exploring relaxin’s effect on tissue remodeling/fibrosis in the human bladder
Authors: Diaz Edward C. , Briggs Mason , Wen Yan , Zhuang Guobing , Wallace Shannon L. , Dobberfuhl Amy D. , Kao Chia-Sui , Chen Bertha C.
Published: April 2020

Background

Relaxin is an endogenous protein that has been shown to have antifibrotic properties in various organ systems. There has been no characterization of relaxin’s role in the human bladder. Our objective was to characterize relaxin receptor expression in the human bladder and assess relaxin’s effect on tissue remodeling/fibrosis pathways in bladder smooth muscle cells.

Methods

Relaxin family peptide receptor 1 (RXFP1) and RXFP2 expression was assessed using quantitative reverse transcriptase-PCR (qRT-PCR) and immunohistochemistry (IHC) on primary bladder tissue. Primary human smooth muscle bladder cells were cultured and stimulated with various concentrations of relaxin. Western blot, qRTPCR, ELISA, and zymogram assays were used to analyze fibrosis/tissue remodeling pathway proteins.

Results

There was universal mRNA transcript detection and protein expression of relaxin receptors in primary bladder specimens. Immunohistochemistry demonstrated RXFP1 and RXFP2 localizing to both urothelial and smooth muscle cell layers of the bladder. 24 h of in vitro relaxin stimulation did not affect mRNA expression of selected proteins in human bladder smooth muscle cells. However, 48 h of in vitro relaxin stimulation resulted in upregulation of active (p = 0.004) and latent (p = 0.027) MMP-2 in cell lysate, and upregulation of active MMP-2 in supernatant (p = 0.04). There was a dose dependent relationship with increasing expression of MMP-2 with increasing relaxin concentration. Relaxin stimulation resulted in decreased levels of active and total TGF-β1 in supernatant and extracellular matrix (p < 0.005 with 100 ng/mL relaxin stimulation).

Conclusions

In the human bladder, relaxin receptors are expressed at the dome and trigone and localize to the urothelium and smooth muscle cell layers. Stimulation of human bladder SMCs with relaxin in vitro affects expression of MMP-2 and TGF-β1.
Ups and downs of drug rehab among women: a qualitative study
Authors: Boroumandfar Zahra , Kianpour Masoud , Afshari Maryam
Published: April 2020

Background

According to recent studies, the number of women drug users is dramatically increasing. However, the information on the issue of drug rehab in women is not sufficient, and there are numerous traditional, organizational, political and cultural barriers to the provision of relevant information in this regard in Iran. This study, thus, aimed to explain the factors influencing the decision of these women to stop drug use.

Methods

This qualitative study was conducted in two rehab camps of Isfahan (in Iran) on July to October 2017. Thirty participants (women drug users) were selected through purposive and theoretical sampling until data saturation was reached. Data collection was conducted through semi-structured interviews. The transcribed interviews were analyzed using conventional content analysis.

Results

Based on the analysis of the obtained results, the women’s experience of the ups and downs of stopping drug use yielded two themes and nine sub-themes. The themes were “the need for emancipation (the deviated path, being abused, compulsive drug use, acquaintance with God, a supportive family)” and “Sinking factors (non-assisting mates, pro-addictive family, unawareness of assisting official organization and non-government organization, woman’s lack of authority, ineffective opportunities)”.

Conclusions

It was concluded that addiction rehab strategies can lead to a brighter life for women drug users only when they are coupled with open-hearted assistance of the families and women specific rehab centers are established to help them meet their specific needs.
Ethyl acetate extract of Kaempferia parviflora inhibits Helicobacter pylori-associated mammalian cell inflammation by regulating proinflammatory cytokine expression and leukocyte chemotaxis
Authors: Nemidkanam Variya , Kato Yuko , Kubota Tetsuo , Chaichanawongsaroj Nuntaree
Published: April 2020

Background

Kaempferia parviflora (KP) has been used in traditional Thai medicine to cure gastrointestinal disorders since ancient times. Helicobacter pylori is an initiating factor in gastric pathogenesis via activation of massive inflammation, the cumulative effect of which leads to gastric disease progression, including gastric carcinogenesis. Accordingly, the effect of a crude ethyl acetate extract of KP (CEAE-KP) on proinflammatory cytokine production and cell chemotaxis was the focus of this study.

Methods

The cytotoxicity of CEAE-KP (8–128 μg/ml) on AGS (gastric adenocarcinoma) cells was determined at 6, 12 and 24 h using an MTT assay. The effect of CEAE-KP on H. pylori-induced interleukin (IL)-8 production by AGS cells was evaluated by ELISA and RT-PCR. The effect of CEAE-KP on monocyte and neutrophil chemotaxis to H. pylori soluble protein (sHP) and IL-8, respectively, was determined using a Boyden chamber assay with THP-1 or HL-60 cells.

Results

CEAE-KP reduced AGS cell viability in a concentration- and time-dependent manner, but at 8–16 μg/ml, it was not cytotoxic after 6–24 h of exposure. Coculture of AGS cells with CEAE-KP at a noncytotoxic concentration of 16 μg/ml and H. pylori reduced IL-8 secretion by ~ 60% at 12 h, which was consistent with the decreased level of mRNA expression, and inhibited neutrophil chemotaxis to IL-8. sHP (100 ng/ml) induced marked monocyte chemoattraction, and this was decreased by ~ 60% by CEAE-KP.

Conclusion

CEAE-KP might serve as a potent alternative medicine to ameliorate the inflammation mediated by H. pylori infection.
No man is an island: spatial clustering and access to primary care as possible targets for the development of new community mental health approaches
Authors: Nascimento M. , Lourenço B. , Coelho I. , Aguiar J. , Lázaro M. , Silva M. , Pereira C. , Neves-Caldas I. , Gomes F. , Garcia S. , Nascimento S. , Pereira G. , Nogueira V. , Costa P. , Nobre A.
Published: April 2020

Background

to understand if patients seen at Centro Hospitalar Psiquiátrico de Lisboa (CHPL) live in geographical clusters or randomly throughout the city, as well as determine their access to the psychiatric hospital and primary care facilities (PCF).

Methods

spatial autocorrelation statistics were performed (queen criterion of contiguity), regarding all patients observed at CHPL in 2017 (at the census subsection level), and considering not only their overall number but also main diagnosis, and admission to the psychiatric ward - voluntary or compulsory.

Distance to the hospital and to the closest PCF was measured (for each patient and the variables cited above), and the mean values were compared.

Finally, the total number of patients around each PCF was counted, considering specified radius sizes of 656 and 1000 m.

Results

All 5161 patients (509 psychiatric admissions) were geolocated, and statistical significance regarding patient clustering was found for the total number (p-0.0001) and specific group of disorders, namely Schizophrenia and related disorders (p-0.007) and depressive disorders (p-0.0002).

Patients who were admitted in a psychiatric ward live farther away from the hospital (p-0.002), with the compulsory admissions (versus voluntary ones) living even farther (p-0.004).

Furthermore, defining a radius of 1000 m for each PCF allowed the identification of two PCF with more than 1000 patients, and two others with more than 800.

Conclusions

as patients seem to live in geographical clusters (and considering PCFs with the highest number of them), possible locations for the development of programs regarding mental health treatment and prevention can now be identified.
Willingness to pay for new medicines: a step towards narrowing the gap between NICE and IQWiG
Authors: Gandjour Afschin
Published: April 2020

Background

The question of how to set the cost-effectiveness threshold for new, innovative medicines is a matter of ongoing controversy. One prominent proposal suggests that the cost-effectiveness threshold adopted by the U.K. National Institute for Health and Care Excellence (NICE) should represent the opportunity cost for the U.K. National Health Service resulting from the adoption of new medicines. The purpose of this article is to compare this proposal for the U.K. with the approach chosen by the Institute for Quality and Efficiency in Health Care (IQWiG) in Germany, which relies on indication-specific cost-effectiveness thresholds.

Main text

The ‘ideal’ NICE and IQWiG surprisingly share the fundamental principle of inferring the willingness to pay from existing care. For this and other reasons, indication-specific thresholds based on IQWiG’s methodology do not lead to more inefficiency at the health system’s level than a generic threshold based on the ‘ideal’ NICE (keeping other conditions the same). Also, applying either decision rule to one country will yield a similar long-term growth in population spending. Assuming that everything else is equal, both decision rules are predicted to decrease long-term expenditure growth. Convergence of the two decision rules would require, among others, ruling out waste in the ‘ideal’ NICE’s approach and, for IQWiG’s approach, using the same relative weights for life expectancy and health-related quality of life as the quality-adjusted-life-year model.

Conclusion

This article shows that both decision rules have notable commonalities in terms of inferring the willingness to pay from existing care and the projected impact on long-term growth in population spending.
Serum amino acid profile in 51 dogs with immunosuppressant-responsive enteropathy (IRE): a pilot study on clinical aspects and outcomes
Authors: Benvenuti Elena , Pierini Alessio , Gori Eleonora , Bartoli Francesco , Erba Paola , Ruggiero Pietro , Marchetti Veronica
Published: April 2020

Background

Lower levels of tryptophan (TRP) have been identified in people with inflammatory bowel disease and in dogs with protein-losing enteropathy (PLE). No data on serum amino acids (AAs) but some on plasma in canine immunosuppressant-responsive enteropathy (IRE) are available. The aim of this study is to compare serum AAs between healthy and IRE dogs, considering clinicopathological variables and follow-up.

Results

Twenty-six healthy control dogs (CD) and 51 IRE dogs were included. IRE was diagnosed after the exclusion of extra-intestinal diseases and food and antibiotic responsive enteropathies. The canine chronic enteropathy clinical activity index (CCECAI) was assessed at presentation and during the clinical follow-up. In CD and IRE dogs, 19 different serum AAs were measured. IRE dogs were classified into responders, partial responders and non-responders, based on CCECAI after 1 month, and divided into PLE and non-PLE, based on albumin level. IRE dogs showed lower L-Tyrosine (TYR), L-Phenylalanine (PHE) and TRP (p < 0.001) and higher L-Serine (SER), L-Glutamic acid (GLU), L-Arginine (p < 0.001), L-Threonine (p = 0.013), Proline (p = 0.044), L-Cysteine (p = 0.003), L-Valine (p = 0.018), L-Lysine (p = 0.01) and L-Isoleucine (p = 0.005) than CDs. PLE dogs showed lower L-Histidine (HIS) (p = 0.008), PHE (p = 0.005) and TRP (p = 0.005) than non-PLE dogs. In IRE dogs, median GLU was significantly lower in dogs with BCS 3/9 than BCS 5/9 category (p = 0.036). Total protein was positively correlated with PHE and TRP (both p = 0.031, r = 0.30) and albumin was positively correlated with HIS (p = 0.025, r = 0.31), PHE and TRP (both p = 0.001, r = 0.46). HIS (p = 0.041), PHE (p = 0.047) and TRP (p = 0.044) concentrations were significantly lower in non-responders than in responders and partial responders.

Conclusions

This study may suggest further investigation on serum, HIS, PHE, TRP and TYR as markers of intestinal disease and proposed HIS, PHE and TRP as prognostic marker for response to therapy.
Impact of baseline symptoms and health status on COPD exacerbations in the FLAME study
Authors: Mackay Alexander J. , Kostikas Konstantinos , Roche Nicolas , Frent Stefan-Marian , Olsson Petter , Pfister Pascal , Gupta Pritam , Patalano Francesco , Banerji Donald , Wedzicha Jadwiga A.
Published: April 2020

Background

COPD is a heterogeneous disease and patients may respond differently to therapies depending on baseline symptom burden.

Methods

This post-hoc analysis from the 52-week FLAME study investigated the impact of baseline symptom burden in terms of health status, dyspnoea, bronchitis status, eosinophil levels and smoking status on the subsequent risk of moderate or severe exacerbations. Health status was measured by St. George’s Respiratory Questionnaire (SGRQ) score (higher ≥46.6 and lower < 46.6) and COPD Assessment Test (CAT) score (higher ≥17 and lower < 17); dyspnoea and bronchitis were assessed via an electronic diary (eDiary). Differential response to once-daily indacaterol/glycopyrronium (IND/GLY) 110/50 μg versus twice-daily salmeterol/fluticasone (SFC) 50/500 μg was assessed.

Results

Data from 3354 patients was analysed. The risk of exacerbations was lower in patients who had less severe health impairment (rate ratio [RR] [95% CI]): SGRQ-C, (0.88 [0.78, 0.99]); CAT, 0.85 [0.75, 0.96]) and lower dyspnoea (0.79 [0.69, 0.90]) at baseline versus those with more severe health impairment and higher dyspnoea, respectively. Compared with SFC, IND/GLY led to better prevention of moderate-to-severe exacerbations in the majority of groups studied.

Conclusion

Patients with more severe health status impairment and greater symptom burden at baseline subsequently experienced more exacerbations in the FLAME study. IND/GLY was overall more effective in preventing exacerbations versus SFC, regardless of baseline symptom burden. Our results suggest that future studies on novel exacerbation therapies should consider targeting patients with higher symptom burden at baseline.

Clinical trial identifier

NCT01782326.