bluuebunny/crossref_metadata_2025_split huggingface dataset:
TIMP-2 secreted by monocyte-like cells is a potent suppressor of invadopodia formation in pancreatic cancer cells
Authors: Benzing Christian , Lam Hoyin , Tsang Chi Man , Rimmer Alexander , Arroyo-Berdugo Yoana , Calle Yolanda , Wells Claire M. 
Published: December 2019

Abstract
Background
Monocytes are a major component of the tumor microenvironment (TME) in pancreatic ductal adenocarcinoma (PDAC). However, the complex interactions between tumor cells and monocytes and their role in tumor invasion have not been fully established.

Methods
To specifically test the impact of interaction on invasive potential two PDAC cell lines PaTu8902 and CFPAC-1 were selected on their ability to form invasive adhesions, otherwise known as invadopodia and invade in a spheroid invasion assay.

Results
Interestingly when the PDAC cells were co-cultured with undifferentiated THP1 monocyte-like cells invadopodia formation was significantly suppressed. Moreover, conditioned media of THP1 cells (CM) was also able to suppress invadopodia formation. Further investigation revealed that both tissue inhibitor of metalloproteinase (TIMP) 1 and 2 were present in the CM. However, suppression of invadopodia formation was found that was specific to TIMP2 activity.

Conclusions
Our findings indicate that TIMP2 levels in the tumour microenvironment may have prognostic value in patients with PDAC. Furthermore, activation of TIMP2 expressing monocytes in the primary tumour could present a potential therapeutic opportunity to suppress cell invasion in PDAC.
DNA methylation of SFRP1, SFRP2, and WIF1 and prognosis of postoperative colorectal cancer patients
Authors: Liu Xinyan , Fu Jinming , Bi Haoran , Ge Anqi , Xia Tingting , Liu Yupeng , Sun Hongru , Li Dapeng , Zhao Yashuang 
Published: December 2019

Abstract
Background
As biomarkers, DNA methylation is used to detect colorectal cancer (CRC) and make assessment of CRC prognosis. The published findings showed the association between the methylation of SFRP1, SFRP2, and WIF1, located in the Wnt signaling pathway, and the prognosis of CRC were not consistent. Our study aimed to explore the potential possibility of SFRP1, SFRP2, and WIF1 concomitant promoter methylation as prognostic biomarkers of postoperative CRC patients.

Methods
As a total of 307 sporadic postoperative CRC patients were followed up, we detected SFRP1, SFRP2, and WIF1 methylation obtained from tumor tissues and adjacent non-tumor tissues respectively on the basis of methylation-sensitive high resolution melting analysis. Univariate and multivariate Cox regressions were carried out so as to assess the potential possibility of SFRP1, SFRP2, and WIF1 promoter methylation as predictors of prognosis. Confounders in our study were controlled by Propensity Score (PS) analysis.

Results
The SFRP1, SFRP2, and WIF1 methylation levels in tumor tissues were significantly higher than that in adjacent non-tumor tissues (P < 0.001). SFRP2 hypermethylation was significantly associated with a favorable clinical outcome at the hazard ratio (HR) of 0.343 [95% confidence intervals (CI): 0.164–0.718, P = 0.005] and 0.410 (95% CI: 0.200–0.842, P = 0.015) in multivariate Cox regression and PS analysis, respectively. Co-hypermethylation of SFRP1 and SFRP2 was significantly associated with a favorable clinical outcome at the HR of 0.333 (95% CI: 0.159–0.694, P = 0.003) and 0.398 (95% CI: 0.192–0.821, P = 0.013) in multivariate Cox regression and PS analysis, respectively. Co-hypermethylation of SFRP1, SFRP2 and WIF1 was significantly associated with a favorable clinical outcome at the HR of 0.326 (95% CI: 0.117–0.908, P = 0.032) and 0.401 (95% CI: 0.146–1.106, P = 0.077) in multivariate Cox regression and PS analysis, respectively.

Conclusions
SFRP1, SFRP2, and WIF1 were frequently hypermethylated in CRC tumor tissues. It was apparent that the promoter hypermethylation of SFRP2 and co-hypermethylation of SFRP1 and SFRP2 might be considered as independent prognostic predictors for survival advantage of postoperative CRC patients.
Significant impact of three-dimensional volumetry of perinephric fat on the console time during robot-assisted partial nephrectomy
Authors: Motoyama Daisuke , Matsushita Yuto , Watanabe Hiromitsu , Tamura Keita , Ito Toshiki , Sugiyama Takayuki , Otsuka Atsushi , Miyake Hideaki 
Published: December 2019

Abstract
Background
To assess the impact of volumetry of perinephric fat (PNF) on the perioperative outcomes of robot-assisted partial nephrectomy (RAPN).

Methods
Between 2016 and 2019, a single surgeon performed RAPN for 128 patients with clinical T1a-b renal tumors at our institution, and the 70 most recent patients were included in this study to minimize the effects of surgical experience. PNF was defined as a fatty area around the kidney within the anatomical structures, including the lateroconal fascia, fusion fascia, psoas muscle, lumbar quadrate muscle and diaphragm, and its volume was calculated based on reconstructed three-dimensional computed tomography images using the SYNAPSE VINCENT system.

Results
In this series, the trifecta and MIC (margin, ischemia and complications) score system outcomes were achieved in 69 (98.6%) and 64 patients (91.4%), respectively. The median PNF volume in the 70 patients was 166.05 cm3, which was significantly correlated with both the body mass index (BMI) and Mayo adhesive probability (MAP) score (correlation coefficient = 0.68 and 0.74, respectively). There was no significant difference in the R.E.N.A.L. nephrometry score, PNF volume or console time during RAPN among 5 groups consisting of 14 consecutive patients. Of several factors examined, the console time was significantly affected by the sex, MAP score and PNF volume, and only the PNF volume was independently associated with the console time.

Conclusion
Even if performed by an experienced robotic surgeon beyond the initial learning curve, the PNF volume may influence the console time during RAPN.
Trueness of CAD/CAM digitization with a desktop scanner – an in vitro study
Authors: Joós-Kovács G. , Vecsei B. , Körmendi Sz. , Gyarmathy V. A. , Borbély J. , Hermann P. 
Published: December 2019

Abstract
Background
Desktop scanners are devices for digitization of conventional impressions or gypsum casts by indirect Computer-Aided Design/Computer-Assisted Manufacturing (CAD/CAM) in dentistry. The purpose of this in vitro study was: 1, to investigate whether virtual models produced by the extraoral scanner have the same trueness as sectioned casts; and 2, to assess if digitization with an extraoral scanner influences the surface information.

Methods
A polimethyl-methacrilic acid (PMMA) cast and a reference scanner (TwoCam 3D, SCAN technology A/S, Ringsted, Denmark; field of view 200 mm, resolution 0.1 mm ± 0.025 mm) were used to create the reference data in standard tessellation format (STL). According to the extraoral CAD/CAM digitization steps, impressions, mastercasts, and sectioned casts were made, and STL files were generated with the reference scanner. The pivotal point of the study was to digitalize these sectioned casts with the extraoral scanner (Straumann CARES Scan CS2 Visual 8.0 software, InstitutStraumann AG, Basel, Switzerland) and STL files were exported. Virtual caliper measurements were performed. Absolute deviations were compared using multilevel mixed-effects linear regression. Relative distortions were calculated with mean absolute errors and reference values.

Results
Differences were observed in measurements of tooth sizes. All four prepared teeth were affected. No relationship was observed in relative deviations. Absolute differences between all the indirect digitization steps considering arch distances were: impressions, − 0.004 mm; mastercasts, 0.136 mm; sectioned casts, − 0.028 mm; and extraoral scanner, − 0.089 mm. Prepared dies on the virtual casts (extraoral scanner) were closer to each other than those on the sectioned gypsum casts. Relative deviation calculations revealed no relationship with the position of the dies in the arch.

Conclusion
The trueness of the virtual models generated by the extraoral scanner system used in this study was different from the dimensions of the sectioned casts. The digitization of gypsum casts changes both the dimensions of dies and the distances between the dies. The virtual casts had smaller distances than any distances measured at previous steps. Either bigger dies or longer distances did not result in greater distortions. We cannot, however, generalize our results to all scanners available on the market, because they might give different results.
A 13-Week Repeated Oral Dose Toxicity Study of ChondroT in Sprague-Dawley Rats
Authors: Jeong Jiwon , Bae Kiljoon , Kim Jihoon , Choi Chanhun , Na Changsu , Park Myeongkyu , Kim Youngran , Seo Chang-Seob , Kim Seon-Jong 
Published: December 2019

Abstract
Background
ChondroT, a new herbal medication, consists of Angelica grosseserrata Maxim., Lonicera japonica Thunb., Angelica gigas Nakai, Clematis terniflora var. manshurica (Rupr.) Ohwi, and Phellodendron amurense Rupr. (6:4:4:4:3). Our previous studies have shown that ChondroT exhibits significant anti-arthritic and anti-inflammatory effects. In this study, we aimed to assess the toxicological safety assessment of ChondroT.

Methods
This study was designed to assess the safety of ChondroT after repeated oral administration.
Male and female Sprague-Dawley rats were treated with ChondroT at oral doses of 0, 500, 1000, and 2000 mg/kg for 13 weeks. Mortality, clinical signs, body weight changes, food consumption, ophthalmological findings, urinalysis, hematological and blood-chemical parameters, necropsy findings, organ weights, and histological markers were recorded throughout the study period. Rats were also monitored for an additional 4 weeks to determine the recovery time.

Results
No death occurred and no significant changes in food consumption, ophthalmologic findings, and urinalysis were found. Although there were alterations in clinical signs, body weights, hematological parameters, blood-chemical parameters, necropsy findings, organ weights, and histological markers, they were not considered to be toxicologically significant.

Conclusions
The results suggest that the no-observed adverse effects level (NOAEL) was 2000 mg/kg/day for the test substance. ChondroT, a new complex herbal medication composed of five plants, can therefore be used safely at the NOAEL.
A new single nucleotide polymorphism affects the predisposition to thoracic ossification of the posterior longitudinal ligament
Authors: Wang Peng , Teng Ze , Liu Xiaoguang , Liu Xiao , Kong Chao , Lu Shibao 
Published: December 2019

Abstract
Background
Thoracic ossification of the posterior longitudinal ligament (T-OPLL) is one of the common factors that cause thoracic spinal stenosis, which results in intractable myelopathy and radiculopathy. Our previous study first reported rs201153092A site mutation in the collagen 6A1 (COL6A1) gene as a potentially pathogenic locus for T-OPLL. We aimed to determine whether the rs201153092A site mutation causes abnormal expression of the COL6A1 in Han Chinese patients with T-OPLL and whether this locus is also associated with cervical-OPLL.

Methods
Peripheral blood was collected from a total of 60 patients with T-OPLL disease (30 patients carrying the rs201153092A site mutation in COL6A1 and 30 wild-type patients) and 400 northern Chinese individuals (200 cervical-OPLL patients and 200 control subjects) using the Sequenom system. The expression of COL6A1 was analyzed by enzyme-linked immunosorbent assay, reverse transcription-quantitative polymerase chain reaction, and Western blotting.

Results
rs201153092A mutation resulted in markedly increased COL6A1 gene expression levels in peripheral blood samples. The allele frequency and genotype frequency results showed that this locus is no difference between cervical-OPLL patients and controls.

Conclusions
The rs201153092A site mutation of COL6A1 can significantly increase the expression of COL6A1. The COL6A1 gene rs201153092A site polymorphism is a potential pathogenic mutation in T-OPLL disease, which may be only associated with the occurrence of T-OPLL.
Expanding the clinical and genetic spectrum of Heimler syndrome
Authors: Gao Feng-Juan , Hu Fang-Yuan , Xu Ping , Qi Yu-He , Li Jian-Kang , Zhang Yong-Jin , Chen Fang , Chang Qing , Song Fang , Shen Si-Mai , Xu Ge-Zhi , Wu Ji-Hong 
Published: December 2019

Abstract
Background
Heimler syndrome (HS) is a rare hereditary systemic disorder, partial clinically overlapping with Usher syndrome. So far, our knowledge of HS is very limited, many cases are misdiagnosed or may not even be diagnosed at all. This study aimed to analyze the clinical and genetic characteristics of HS, and to evaluate potential phenotype–genotype correlations.

Results
Two HS cases caused by PEX1 mutations were identified, and a novel likely pathogenic mutation, PEX1 c.895_896insTATA, was found. The main ophthalmic finding of the two patients was consistent with retinitis pigmentosa accompanied by cystoid macular edema, but short axial length and hyperopia were also observed as two previously unreported ocular phenotypes. Analysis of the literature showed that of the 29 HS patients previously reported, 12 had PEX6 mutations, 10 had PEX1 mutations, two had PEX26 mutations, and the remaining patients were not genetically tested. Three novel genotype–phenotype correlations were revealed from analysis of these patients. First, most genotypes of every HS patient include at least one missense variant; second, at least one mutation in PEX1 or PEX6 gene affects the AAA-ATPase region in every HS patient with retinal dystrophy, suggesting AAA-ATPase region is a hypermutable region in patients with a retinal dystrophy; third, there are no significant differences between PEX1-, PEX6-, and PEX26-associated phenotypes.

Conclusion
Next-generation sequencing is important for the diagnosis of HS. This study expands the clinical and genetic spectrum of HS, and provides additional insights into genotype–phenotype correlations, which is vital for accurate clinical practice, genetic counseling, and pathogenesis studies.
Effect of high-dose vitamin C therapy on severe burn patients: a nationwide cohort study
Authors: Nakajima Mikio , Kojiro Morita , Aso Shotaro , Matsui Hiroki , Fushimi Kiyohide , Kaita Yasuhiko , Goto Hideaki , Yamaguchi Yoshihiro , Yasunaga Hideo 
Published: December 2019

Abstract
Background
Vitamin C is a well-documented antioxidant that reduces oxidative stress and fluid infusion in high doses; however, the association between high-dose vitamin C and reduced mortality remains unclear. This study evaluates the effect of high-dose vitamin C in severe burn patients under two varying thresholds.

Methods
We enrolled adult patients with severe burns (burn index ≥ 15) who were registered in the Japanese Diagnosis Procedure Combination national inpatient database from 2010 to 2016. Propensity score matching was performed between patients who received high-dose vitamin C within 1 day of admission (vitamin C group) and those who did not (control group). High-dose vitamin C was defined as a dosage in excess of 10 g or 24 g within 2 days of admission. The primary outcome was in-hospital mortality.

Results
Eligible patients (n = 2713) were categorized into the vitamin C group (n = 157) or control group (n = 2556). After 1:4 propensity score matching, we compared 157 and 628 patients who were administered high-dose vitamin C (> 10-g threshold) and controls, respectively. Under this particular threshold, high-dose vitamin C therapy was associated with reduced in-hospital mortality (risk ratio, 0.79; 95% confidence interval, 0.66–0.95; p = 0.006). In contrast, in-hospital mortality did not differ between the control and high-dose vitamin C group under the > 24-g threshold (risk ratio, 0.83; 95% confidence interval, 0.68–1.02; p = 0.068).

Conclusions
High-dose vitamin C therapy was associated with reduced mortality in patients with severe burns when used under a minimum threshold of 10 g within the first 2 days of admission. While “high-dose” vitamin C therapy lacks a universal definition, the present study reveals that different “high-dose” regimens may yield improved outcomes.
Increasing sensor reliability through confidence attribution
Authors: Scheffel Roberto M. , Fröhlich Antônio A. 
Published: December 2019

AbstractThe reliability of wireless sensor networks (WSN) is getting increasing importance as this kind of networks are becoming the communication base for many cyber-physical systems (CPS). Such systems rely on sensor data correctness to make decisions; therefore, faulty data can lead such systems to take wrong actions. Errors can be originated by sensor’s hardware failures or software bugs and also from the intentional interference of intruders. The gateways that connect such WSN to the Internet are natural intruders’ targets as they usually run conventional operating systems and communication protocols. This work proposes a confidence attribution scheme, based on lightweight predictors running on the sensors. The solution also proposes a parameterizable formula, in order to stamp every value sent by a sensor with aconfidence level, calculated upon the values of a subset of correlated sensors. This work also presents an algorithm that can identify a defective sensor into its subset. The use of predictors and confidence attribution are proposed as the basis of a mechanism that increases the WSN resilience against sensor failure or bad data injection by intruders. Several simulations were performed to evaluate the detection efficiency against different types of sensor errors. This work also analyses mechanisms to deal with concept drifts in the WSN lifetime.
Iris metastasis as the initial presentation of upper gastrointestinal tract carcinoma: a case report
Authors: Siddiqui M. A. Rehman , Hussain Syed Zohaib Maroof , Mubarak Muhammed 
Published: December 2019

Abstract
Background
We report a case of a patient with iris metastasis as the initial manifestation of a systemic cancer: upper gastrointestinal tract carcinoma.

Case presentation
A 24-year-old Asian man presented to our hospital with complaints of red left eye, decreased visual acuity, pain, and photophobia for about 3 weeks with no prior history of cancer or any other medical abnormality. Ocular examination showed a pinkish white lesion on the superonasal part of the iris. The patient’s intraocular pressure was progressively increasing despite medications, followed by lymphadenopathy 4 weeks later. Comprehensive examination was performed along with a complete systemic workup, which detected systemic malignancy. Histopathology and immunohistochemistry revealed signet ring cells, which indicated an upper gastrointestinal tract tumor as a primary source of iris metastasis. The systemic condition of the patient deteriorated rapidly thereafter and led to his death in the 12th week of the disease.

Conclusion
A red eye with iris lesions in otherwise healthy individuals should be considered as a possible initial manifestation of underlying systemic malignancy. Prompt referral of such patients to an oncologist is warranted.
Graves disease-induced thrombotic thrombocytopenic purpura: a case report
Authors: Chaughtai Saira , Khan Ijaz , Gupta Varsha , Chaughtai Zeeshan , Ong Raquel , Asif Arif , Hossain Mohammad A. 
Published: December 2019

Abstract
Background
Thrombotic thrombocytopenic purpura is an autoimmune disease that carries a high mortality. Very few case reports in the literature have described a relationship between Graves disease and thrombotic thrombocytopenic purpura. We present a case of a patient with Graves disease who was found to be biochemically and clinically hyperthyroid with concurrent thrombotic thrombocytopenic purpura.

Case presentation
Our patient was a 30-year-old African American woman with a history of hypertension and a family history of Graves disease who had recently been diagnosed with hyperthyroidism and placed on methimazole. She presented to our hospital with the complaints of progressive shortness of breath and dizziness. Her vital signs were stable. On further evaluation, she was diagnosed with thrombotic thrombocytopenic purpura, depending on clinical and laboratory results, and also was found to have highly elevated free T4 and suppressed thyroid-stimulating hormone. She received multiple sessions of plasmapheresis and ultimately had a total thyroidectomy. The patient’s hospital course was complicated by pneumonia and acute respiratory distress syndrome. Her platelets stabilized at approximately 50,000/μl, and her ADAMTS13 activity normalized despite multiple complications. The patient ultimately had a cardiac arrest with pulseless electrical activity and died despite multiple attempts at cardiopulmonary resuscitation.

Conclusion
Graves disease is an uncommon trigger for the development of thrombotic thrombocytopenic purpura, and very few cases have been reported thus far. Therefore, clinicians should be aware of this association in the appropriate clinical context to comprehensively monitor hyperthyroid patients during treatment.
The vaginal and fecal microbiomes are related to pregnancy status in beef heifers
Authors: Deng Feilong , McClure Maryanna , Rorie Rick , Wang Xiaofan , Chai Jianmin , Wei Xiaoyuan , Lai Songjia , Zhao Jiangchao 
Published: December 2019

AbstractBackgroundThe greatest impact on profitability of a commercial beef operation is reproduction. However, in beef heifers, little is known about the vaginal and fecal microbiota with respect to their relationship with fertility. To this end, we followed heifers through gestation to examine the dynamics of vaginal and fecal microbial composition throughout pregnancy.ResultsHeifers were exposed to an estrus synchronization protocol, observed over a 12-day period, artificially inseminated 12 h to 18 h after observed estrus, and subsequently exposed to bulls for a 50-day breeding season. Vaginal samples were taken at pre-breeding (n = 72), during the first (n = 72), and second trimester (n = 72) for all individuals, and third trimester for individuals with confirmed pregnancies (n = 56). Fecal samples were taken at pre-breeding (n = 32) and during the first trimester (n = 32), including bred and open individuals. Next generation sequencing of the V4 region of the16S rRNA gene via the Illumina MiSeq platform was applied to all samples. Shannon indices and the number of observed bacterial features were the same in fecal samples. However, significant differences in vaginal microbiome diversity between gestation stages were observed. No differences in beta-diversity were detected in vaginal or fecal samples regarding pregnancy status, but such differences were seen with fecal microbiome over time. Random Forest was developed to identify predictors of pregnancy status in vaginal (e.g.,Histophilus, Clostridiaceae,Campylobacter) and fecal (e.g., Bacteroidales,Dorea) samples.ConclusionsOur study shows that bovine vaginal and fecal microbiome could be used as biomarkers of bovine reproduction. Further experiments are needed to validate these biomarkers and to examine their roles in a female’s ability to establish pregnancy.