bluuebunny/crossref_metadata_2025_split huggingface dataset:
NMDA receptor-mediated CaMKII/ERK activation contributes to renal fibrosis
Authors: Zhou Jingyi , Liu Shuaihui , Guo Luying , Wang Rending , Chen Jianghua , Shen Jia 
Published: September 2020

Abstract
Background
This study aimed to understand the mechanistic role of N-methyl-D-aspartate receptor (NMDAR) in acute fibrogenesis using models of in vivo ureter obstruction and in vitro TGF-β administration.

Methods
Acute renal fibrosis (RF) was induced in mice by unilateral ureteral obstruction (UUO). Histological changes were observed using Masson’s trichrome staining. The expression levels of NR1, which is the functional subunit of NMDAR, and fibrotic and epithelial-to-mesenchymal transition markers were measured by immunohistochemical and Western blot analysis. HK-2 cells were incubated with TGF-β, and NMDAR antagonist MK-801 and Ca2+/calmodulin-dependent protein kinase II (CaMKII) antagonist KN-93 were administered for pathway determination. Chronic RF was introduced by sublethal ischemia–reperfusion injury in mice, and NMDAR inhibitor dextromethorphan hydrobromide (DXM) was administered orally.

Results
The expression of NR1 was upregulated in obstructed kidneys, while NR1 knockdown significantly reduced both interstitial volume expansion and the changes in the expression of α-smooth muscle actin, S100A4, fibronectin, COL1A1, Snail, and E-cadherin in acute RF. TGF-β1 treatment increased the elongation phenotype of HK-2 cells and the expression of membrane-located NR1 and phosphorylated CaMKII and extracellular signal–regulated kinase (ERK). MK801 and KN93 reduced CaMKII and ERK phosphorylation levels, while MK801, but not KN93, reduced the membrane NR1 signal. The levels of phosphorylated CaMKII and ERK also increased in kidneys with obstruction but were decreased by NR1 knockdown. The 4-week administration of DXM preserved renal cortex volume in kidneys with moderate ischemic–reperfusion injury.

Conclusions
NMDAR participates in both acute and chronic renal fibrogenesis potentially via CaMKII-induced ERK activation.
The relationships between three-axis accelerometer measures of physical activity and motor symptoms in patients with Parkinson’s disease: a single-center pilot study
Authors: Ito Hiroto , Yokoi Daichi , Kobayashi Rei , Okada Hisashi , Kajita Yasukazu , Okuda Satoshi 
Published: September 2020

Abstract
Background
Various wearable devices for objectively evaluating motor symptoms of patients with Parkinson’s disease (PD) have been developed. Importantly, previous studies have suggested protective effects of physical activity in PD. However, the relationships between conventional clinical ratings for PD and three-axis accelerometer measures of physical activity (e.g., daily physical activity levels [PAL] or metabolic equivalents of task [METs]) are still unclear, particularly for METs. In the current study, we sought to elucidate these relationships on a daily basis, and to clarify optimal predictors for clinical states on a 30-min basis.

Methods
Patients who were hospitalized for adjustment of drugs or deep brain stimulation were enrolled. Using waist-worn three-axis accelerometers, PAL and METs parameter data were obtained and compared with UPDRS-3[On] and symptom diary data. We extracted data from the patients’ best and worst days, defined by the best and worst UPDRS-3[On] scores, respectively. Thus, 22 data sets from 11 patients were extracted. We examined the correlations and produced scatter plots to represent the relationships, then investigated which METs parameters and activity patterns were the best predictors for “On” and “dyskinesia”.

Results
The parameter “mean METs value within the 95–92.5 percentile range on a day (95–92.5 percentile value)” exhibited the strongest correlation with conventional daily clinical ratings (Rho: − 0.799 for UPDRS-3[On], 0.803 for On hours [p < 0.001]). Scatter plots suggested that PAL tended to have higher values in patients with involuntary movement. However, METs parameters focusing on higher METs seemed to alleviate this tendency. We clarified that “time over 2.0 METs” and “time over 1.5 METs” could be predictors for “On” and “dyskinesia” on a 30-min basis, respectively (AUROC: 0.779 and 0.959, 95% CI: 0.733–0.824 and 0.918–1.000). The specificity and sensitivity of the optimal activity pattern for “On” were 0.858 and 0.621.

Conclusions
This study suggested feasible activity patterns and METs parameters for objective evaluation of motor symptoms on a 30-min or daily basis. Three-axis accelerometer measures focusing on higher METs may be appropriate for evaluating physical activity. Further larger-scale studies are necessary to clarify the validity, reliability, and clinical utility of these objective measures.
Walking in pregnancy and prevention of insomnia in third trimester using pedometers: study protocol of Walking_Preg project (WPP). A randomized controlled trial
Authors: Amezcua-Prieto C. , Naveiro-Fuentes M. , Arco-Jiménez N. , Olmedo-Requena R. , Barrios-Rodríguez R. , Vico-Zúñiga I. , Manzanares Galán S. , Mozas-Moreno J. , Jiménez-Moleón J. J. , Gallo-Vallejo J. L. 
Published: September 2020

AbstractBackgroundPrevious studies in pregnancy have not focused in evaluating the effect of walking during pregnancy and prevention of insomnia. Our general objective is to determine the effect of a walking program in preventing the appearance of insomnia in the third trimester of pregnancy, increasing sleep quality and improving quality of life throughout pregnancy.MethodsRandomized Controlled trial in parallel in healthy sedentary pregnant women (n = 265), Walking_Preg Project (WPP), from university hospital in Granada, Spain. At 12th gestational week (GW), they will be invited to participate and randomly assigned to one of the three arms of study: the intervention group I1 (pedometer, goal of 11,000 steps/day), intervention group I2 (pedometer, no goal) and control (no pedometer). Duration of intervention: 13–32 GW. At 12th, 19th and 31st GW the average steps/day will be measured in groups I1 and I2. At 13th, 20th and 32nd GW, Athens Insomnia Scale (AIS), Pittsburgh Sleep Quality Index (PSQI), Adherence to Mediterranean Diet (AMD), physical activity (short IPAQ), quality of life (PSI), and consumption of toxic substances (caffeine, illegal drugs, alcohol and tobacco) will be collected. Student t test or Mann-Whitney U will be used to compare 19th and 31st GW mean of daily steps between I1 and I2 groups. To compare differences between groups in terms of frequency of insomnia/quality of life for each trimester of pregnancy, Pearson’s Chi-square test or Fisher’s exact test will be used. To determine differences in hours of sleep and quality of sleep throughout each trimester of pregnancy, analysis of variance or Friedman test will be used. McNemar-Bowker test will be used to assess differences in life quality in pre-post analyses in the 3 arms. We will use Stata 15 statistical software.Discussionpromoting walking in second half of pregnancy through use of pedometer and health pre-registration of a goal to be achieved –'10,000–11,000 steps a day’– should prevent appearance of insomnia in third trimester, will increase sleep quality and quality of life in pregnant women.Trial registrationClinicalTrials.govIdentifier:NCT03735381. Registered 8th November, 2018.
Sulindac plus a phospholipid is effective for polyp reduction and safer than sulindac alone in a mouse model of colorectal cancer development
Authors: Davis Jennifer S. , Kanikarla-Marie Preeti , Gagea Mihai , Yu Patrick L. , Fang Dexing , Sebastian Manu , Yang Peiying , Hawk Ernest , Dashwood Roderick , Lichtenberger Lenard M. , Menter David , Kopetz Scott 
Published: September 2020

Abstract
Background
Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and sulindac are effective for colorectal cancer prevention in humans and some animal models, but concerns over gastro-intestinal (GI) ulceration and bleeding limit their potential for chemopreventive use in broader populations. Recently, the combination of aspirin with a phospholipid, packaged as PL-ASA, was shown to reduce GI toxicity in a small clinical trial. However, these studies were done for relatively short periods of time. Since prolonged, regular use is needed for chemopreventive benefit, it is important to know whether GI safety is maintained over longer use periods and whether cancer prevention efficacy is preserved when an NSAID is combined with a phospholipid.

Methods
As a first step to answering these questions, we treated seven to eight-week-old, male and female C57B/6 Apcmin/+ mice with the NSAID sulindac, with and without phosphatidylcholine (PC) for 3-weeks. At the end of the treatment period, we evaluated polyp burden, gastric toxicity, urinary prostaglandins (as a marker of sulindac target engagement), and blood chemistries.

Results
Both sulindac and sulindac-PC treatments resulted in significantly reduced polyp burden, and decreased urinary prostaglandins, but sulindac-PC treatment also resulted in the reduction of gastric lesions compared to sulindac alone.

Conclusions
Together these data provide pre-clinical support for combining NSAIDs with a phospholipid, such as phosphatidylcholine to reduce GI toxicity while maintaining chemopreventive efficacy.
Nomogram for individually predicting overall survival in rectal neuroendocrine tumours
Authors: Feng Xingyu , Wei Gengzhou , Wang Wei , Zhang Yu , Zeng Yujie , Chen Minhu , Chen Ye , Chen Jie , Zhou Zhiwei , Li Yong 
Published: September 2020

Abstract
Background
This study aimed to develop a nomogram that predicts the overall survival (OS) of rectal neuroendocrine tumours (NETs).

Methods
We retrospectively analysed 310 patients with rectal neuroendocrine tumours in 5 hospitals in southern China. All of the patients were assigned to the training set. A multivariable analysis using Cox proportional hazards regression was performed using the training set, and a nomogram was constructed. It was validated on a dataset obtained from the Surveillance, Epidemiology, and End Result (SEER) database of America (n = 547).

Results
In the training set, the nomogram exhibited improved discrimination power compared with the WHO grade guidelines (Herrell’s C-index, 0.872 vs 0.794; p < 0.001) and was also better than the seventh AJCC TNM classification (Herrell’s C-index, 0.872 vs 0.817; p < 0.001). In the SEER validation dataset, the discrimination was also excellent (C-index, 0.648 vs 0.583, p < 0.001 and 0.648 vs 0.603, p = 0.016, respectively, compared with G grade and TNM classification). Calibration of the nomogram predicted individual survival corresponding closely with the actual survival.

Conclusions
We developed a nomogram predicting 1- and 3-year OS of patients with rectal neuroendocrine tumours. Validation revealed excellent discrimination and calibration, suggesting good clinical utility.
Influence of automated visual field testing on intraocular pressure
Authors: Bertaud Samuel , Skarbek Borowski Elisabeth , Abbas Rachid , Baudouin Christophe , Labbé Antoine 
Published: September 2020

Abstract
Background
To evaluate the influence of automated visual field (VF) testing on intraocular pressure (IOP) in patients with ocular hypertension (OHT) or glaucoma.

Methods
We conducted a prospective observational study in the glaucoma department at Quinze-Vingts National Ophthalmology Hospital in Paris. Ninety-five right eyes of 95 patients followed for glaucoma or OHT were included. IOP was measured three times using a Nidek NT-510 non-contact tonometer within a maximum of 5 min before and after VF testing. Sub analyses using logistic regression analysis were performed to evaluate the impact of gender, age, central corneal thickness (CCT), mean deviation (MD) of the VF, VF test duration and filtration surgery on IOP fluctuations.

Results
There was no significant change in IOP after VF testing, with IOP’s 15.14 ± 4.00 mmHg before and 14.98 ± 3.33 mmHg after the VF (P = 0.4). The average change in IOP was 0.15 ± 1.82 mmHg. Using multivariate analysis, no effect of the VF test on IOP was found (global model fit R2 = 0.12), whether based on duration of the VF test (P = 0.18) or the MD (P = 0.7) after adjustment for age, gender, CCT and history of glaucoma surgery. Similarly, there was no significant difference within different types of glaucoma, including open-angle glaucoma (P = 0.36), chronic angle closure glaucoma (P = 0.85) and OHT (P = 0.42). The subgroup of patients with an IOP elevation ≥2 mmHg had a significantly higher VF test duration (P = 0.002).

Conclusion
VF testing does not influence IOP as measured with a non-contact tonometer.
Knowledge gain and usage of knowledge learned during internet-based CBT treatment for adolescent depression - a qualitative study
Authors: Berg Matilda , Malmquist Anna , Rozental Alexander , Topooco Naira , Andersson Gerhard 
Published: September 2020

Abstract
Background
The role of explicit learning of treatment content in internet-based cognitive-behavioural treatment (ICBT) is an emerging field of research. The objective of this study was to explore clients experiences of their ICBT treatment for depression with a focus on knowledge gain and usage of knowledge learned during treatment.

Methods
A strategic sample of ten adolescents, aged between 15 and 19 years, who had received ICBT for major depression within a clinical controlled trial were recruited for the study. Semi-structured interviews were conducted 6 months following trial completion. Data were transcribed and analysed using thematic analysis. The participants had a general adherence rate of 6–8 opened modules out of 8 possible.

Results
Two main themes were identified; “Active agents of CBT” and “Passive agents of CBT”, with each theme consisting of three and two sub-themes. Active agents of CBT reflect a tendency to specifically remember and actively apply specific CBT principles in present life situations. Passive agents of CBT reflect a tendency to remember CBT treatment principles vaguely and express a passive or reactive usage of learned therapy content.

Conclusion
The findings suggest that young clients can remember and apply CBT principles 6 months after their treatment. However, while experiencing benefits of treatment, clients recall and application of treatment strategies vary. The study emphasizes the importance of exploring client recall of CBT components and how valuable it is to explicitly remember contents of a treatment in order to improve and maintain improvement. Further studies on the role of knowledge and memory of ICBT for adolescent populations are warranted.
Association between time spent in the Russian Federation and late presentation for HIV among Tajikistani migrants
Authors: Bromberg Daniel J. , Tate Mary M. , Alaei Kamiar , Karimov Saifuddin , Saidi Dilshod , Alaei Arash 
Published: September 2020

Abstract
Background
Between 700 thousand and 1.2 million citizens of Tajikistan currently live in the Russian Federation, one of the only countries where the HIV epidemic continues to worsen. Given the previously reported barriers to healthcare access for migrants to the Russian Federation, and the rapidly expanding HIV epidemic in Eastern Europe and Central Asia, this present study set out to determine whether these barriers impact late presentation with HIV among Tajikistani migrants upon their return to Tajikistan.

Method
This study uses data from the Tajikistan Ministry of Health surveillance system (2006 – 2019). At time of diagnosis, patients are interviewed by staff of AIDS centers, and doctors complete routine intake forms and complete medical exams. Descriptive characteristics of migrants with HIV who had lived in the Russian Federation (n=503) were calculated and compared with those of non-migrants with HIV (n=9519). Missing data were imputed using multiple imputation (predictive means matching, logistic regression imputation, and polytomous regression imputation). Two logistic models were created to model the probability of late presentation for HIV. The first model shows unadjusted associations between predictor variables and late presentation for HIV. The second model shows multivariable associations between significant study variables identified in the univariate model, and late presentation.

Results
Compared to non-migrants, migrants with HIV are more likely to be from Gorno-Badakhshan region, are less likely to use illicit drugs, and are more likely to have purchased the services of sex workers. The unadjusted logistic model found that for every year spent in the Russian Federation, the risk of late presentation for a Tajikistani migrant with HIV increases by 4.0% (95% CI: 0.3-7.7). The multivariate model showed that when age, sex, and region of origin are held constant, the risk of late presentation for a Tajikistani migrant with HIV increases by 4.0% (95% CI: 0.1-7.8) for each year spent in the Russian Federation.

Conclusion
The results of this paper suggest that if the Russian Federation were to loosen its restrictions on HIV care for foreign nationals, it might improve the treatment outcomes of migrant laborers. As this analysis is only correlational in nature, further research is needed to explicate the causal pathways of the associations found in the present analysis.
Investigating the knowledge of and public attitudes towards genetic testing within the Visegrad countries: a cross-sectional study
Authors: Bíró Klára , Dombrádi Viktor , Fekete Zita , Bányai Gábor , Boruzs Klára , Nagy Attila , Ádány Róza 
Published: September 2020

Abstract
Background
Previous studies have investigated various factors that can determine the attitudes of the citizens considering genetic testing. However, none of them investigated how these attitudes may differ between the Visegrad countries.

Methods
In this cross-sectional study a questionnaire developed by Dutch researchers was translated and used in Hungary, Slovakia, Czechia and Poland. In each country 1000 adult citizens were asked on the topics of personal benefits regarding genetic tests, genetic determinism, and finally, the availability and usage of genetic testing. Multivariate robust regression model was created including several possible influencing factors (such as age, sex, education, marital status, religiousness, and having a genetic test within the nuclear family) to identify the possible differences between the four countries.

Results
The Hungarian citizens had the most positive opinion on the personal benefits of genetic testing followed by the Czech, Slovak and Polish. All differences were significant in this regard. Considering genetic determinism, the Slovak citizens had a significantly firmer belief in this issue compared to the Hungarians. No other significant differences were observed in this domain. On the topic of the availability and use of genetic testing the Hungarian citizens had the most accepting opinion among the four countries, followed by the Czech citizens. In this domain the Polish and Slovak answers did not differ significantly from each other.

Conclusions
Significant differences were observed even when considering various confounding effects. As the underlying reasons for these discrepancies are unknown, future studies should investigate this enigma among the four countries.
Contact pressure distribution of the hip joint during closed reduction of developmental dysplasia of the hip: a patient-specific finite element analysis
Authors: Zhang Zhiqiang , Sui Dashan , Qin Haiyi , Li Hai , Zhang Ziming 
Published: September 2020

Abstract
Background
Developmental dysplasia of the hip (DDH) is the most common deformity of the lower extremity in children. The biomechanical change during closed reduction (CR) focused on cartilage contact pressure (CCP) has not been studied. Thereby, we try to provide insight into biomechanical factors potentially responsible for the success of CR treatment sand complications by using finite element analysis (FEA) for the first time.

Methods
Finite element models of one patient with DDH were established based on the data of MRI scan on which cartilage contact pressure was measured. During CR, CCP between the femoral head and acetabulum in different abduction and flexion angles were tested to estimate the efficacy and potential risk factors of avascular necrosis (AVN) following CR.

Results
A 3D reconstruction by the FEA method was performed on a 16 months of age girl with DDH on the right side. The acetabulum of the involved side showed a long, narrow, and “flat-shaped” deformity, whereas the femoral head was smaller and irregular compared with the contralateral side. With increased abduction angle, the stress of the posterior acetabulum increased significantly, and the stress on the lateral part of the femoral head increased as well. The changes of CCP in the superior acetabulum were not apparent during CR. There were no detectable differences in terms of pressure on the femoral head.

Conclusions
Severe dislocation (IHDI grade III and IV) in children showed a high mismatch between the femoral head and acetabulum. Increased abduction angle corresponded with high contact pressure, which might relate to AVN, whereas increased flexion angle was not. Enhanced pressure on the lateral part of the femoral head might increase the risk of AVN.
A prospective study on cancer risk after total hip replacements for 41,402 patients linked to the Cancer registry of Norway
Authors: Dybvik Eva , Furnes Ove , Havelin Leif I. , Fosså Sophie D. , Trovik Clement , Lie Stein Atle 
Published: September 2020

Abstract
Background
Concerns have been raised that implants used in total hip replacements (THR) could lead to increased cancer risk. Several different materials, metals and fixation techniques are used in joint prostheses and different types of articulation can cause an increased invasion of particles or ions into the human body.

Methods
Patients with THR registered in the Norwegian Arthroplasty Register during 1987–2009 were linked to the Cancer registry of Norway. Patients with THR due to osteoarthritis, under the age of 75 at time of surgery, were included. Standardized incidence ratios (SIR) were applied to compare cancer risk for THR patients to the general population. Types of THR were divided into cemented (both components), uncemented (both components), and hybrid (cemented femoral and uncemented acetabular components). To account for selection mechanisms, time dependent covariates were applied in Cox-regression, adjusting for cancer risk the first 10 years after surgery. The analyses were adjusted for age, gender and if the patient had additional THR-surgery in the same or the opposite hip. The study follows the STROBE guidelines.

Results
Comparing patients with THR to the general population in Norway we found no differences in cancer risk. The overall SIR for the THR-patients after 10 years follow-up was 1.02 (95% CI: 0.97–1.07). For cemented THR, the SIR after 10 years follow-up was 0.99 (95% CI: 0.94–1.05), for uncemented, 1.16 (95% CI: 1.02–1.30), and for hybrid 1.12 (95% CI: 0.91–1.33). Adjusted Cox analyses showed that patients with uncemented THRs had an elevated risk for cancer (hazard ratio: HR = 1.24, 95% CI: 1.05–1.46, p = 0.009) when compared to patients with cemented THRs after 10 years follow-up. Stratified by gender the increased risk was only present for men. The risk for patients with hybrid THRs was not significantly increased (HR = 1.07, 95% CI: 0.85–1.35, p = 0.55) compared to patients with cemented THRs.

Conclusions
THR patients had no increased risk for cancer compared to the general population. We found, however, that receiving an uncemented THR was associated with a small increased risk for cancer compared to cemented THR in males, but that this may be prone to unmeasured confounding.