bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of KNL1 on the proliferation and apoptosis of colorectal cancer cells
Authors: Bai Tianliang , Zhao Yalei , Liu Yabin , Cai Bindan , Dong Ning , Li Binghui 
Published: July 2019

Objective: To identify the expression of kinetochore scaffold 1 ( KNL1) in colorectal tumor tissues and to clarify the role of this gene in the proliferation capability of colorectal cancer cells. Methods: A total of 108 paired colorectal tumor and normal tissue samples were collected from patients with colorectal cancer and subjected to quantitative polymerase chain reaction and immunohistochemistry analyses. Expression levels of KNL1 mRNA and protein were compared between tumor and normal tissues, and KNL1 levels were evaluated in relation to the patients’ tumor differentiation, sex, lymph node metastasis, TNM stage, infiltration depth, age, and tumor location. Survival curves were also constructed and compared between patients with tumor samples with and without KLN1 protein expression. KNL1 was under-expressed in colorectal cancer cells in vitro using lentiviral transfection with short hairpin RNA, and its function was evaluated by proliferation, colony-formation, and apoptosis assays. Expression levels of BUB1 protein were also compared between tumor and normal tissues, and the correlation between KNL1 expression and BUB1 expression in colorectal cancer tissues was examined. Results: KNL1 mRNA and protein were both highly expressed in colorectal tumor tissues compared with paired normal tissues. KNL1 downregulation significantly inhibited colorectal cancer cell proliferation and colony formation, and promoted apoptosis. KNL1 protein expression was significantly associated with tumor differentiation, but not with sex, lymph node metastasis, TNM stage, infiltration depth, age, or tumor location. KNL1 protein expression was also significantly associated with poorer survival. Moreover, there was a significant correlation between KNL1 and BUB1 in colorectal cancer tissues. Conclusions: KNL1 plays an effective role in decreasing apoptosis and promoting the proliferation of colorectal cancer cells, suggesting that its inhibition may represent a promising therapeutic approach in patients with colorectal cancer.
Intravenous immunoglobulin to prevent myasthenic crisis after thymectomy and other procedures can be omitted in patients with well-controlled myasthenia gravis
Authors: Gamez Josep , Salvadó María , Carmona Francesc , de Nadal Miriam , Romero Laura , Ruiz Daniel , Jáuregui Alberto , Martínez Olga , Pérez Javier , Suñé Pilar , Deu María 
Published: July 2019

Background: Myasthenic crisis (MC) is a potentially life-threatening complication of myasthenia gravis. Its precipitating factors include surgical procedures, particularly thymectomy. The role of preoperative intravenous immunoglobulin (IVIg) in preventing MC in patients scheduled for thymectomy and other surgery with general anaesthesia is unknown. Our objective was to test the hypothesis that preoperative IVIg is effective in preventing myasthenic crisis in patients with myasthenia gravis scheduled for surgery under general anaesthesia, including thymectomy. Methods: A prospective, randomized, double-blind, single-centre study was conducted over a 4-year period. The treatment group received IVIg, 0.4 g/kg/day preoperatively for 5 consecutive days, and the placebo group received saline solution under the same conditions. The two groups were age-matched, with similar functional status, and Myasthenia Gravis Foundation of America class. All patients had well-controlled myasthenia gravis with minimal manifestations before surgery. The primary outcome measured was MC. Intubation times, time in the recovery room, number of postoperative complications, and days of hospitalization were the secondary outcomes measured. Results: A total of 47 patients were randomized, 25 to the IVIg group and 22 to placebo. There were 19 men and 28 women, with a mean age of 58.6 years, mean body mass index of 27.8 kg/m2, and mean acetylcholine receptor antibodies of 12.9 nmol/l. The mean forced vital capacity was 84.4%. The mean quantitative myasthenia gravis sum score was 6.3. Ten patients (five in each arm) had a history of MC. Thymectomy was performed in 16 patients. Only one patient in the placebo group presented with MC requiring non-invasive ventilation (but no reintubation) for 6 days. Neither differences between groups in the univariate analysis nor risk factors for MC in the multivariate analysis were found. Conclusions: Preoperative IVIg to prevent MC does not appear to be justified in well-controlled myasthenia gravis patients. This study provides class I evidence that preparation with IVIg to prevent MC is not necessary in well-controlled myasthenia gravis patients scheduled for surgery with general anaesthesia.
A real-world analysis of second-line treatment options in pancreatic cancer: liposomal-irinotecan plus 5-fluorouracil and folinic acid
Authors: Kieler Markus , Unseld Matthias , Bianconi Daniela , Scheithauer Werner , Prager Gerald W. 
Published: July 2019

Background: Nanoliposomal irinotecan (nal-IRI) plus 5-fluorouracil/leucovorin (5-FU/LV) is a novel treatment option for gemcitabine-pretreated metastatic pancreatic adenocarcinoma (PAC) patients, but real-world evidence is rare. Our aim was to determine the effectiveness and tolerability of this regimen in advanced PAC patients and to compare it with oxaliplatin plus fluoropyrimidines in the second-line setting after failure of gemcitabine. Methods: This is a retrospective single-center analysis of all patients who have been treated with nal-IRI plus 5-FU/LV. To compare its effectiveness with other second-line treatment options, all patients who had received oxaliplatin plus fluoropyrimidines after gemcitabine-based chemotherapy were also eligible for analysis. Results: Fifty-two patients were treated with nal-IRI plus 5-FU/LV between April 2016 and August 2018. The median progression-free survival (PFS) was 3.84 months and the median overall survival (OS) was 6.79 months. Median OS from the beginning of the treatment for advanced disease was 19.9 months. Median PFS in patients that received nal-IRI plus 5-FU/LV as second-line treatment after gemcitabine-based chemotherapy was 4.49 months whereas median PFS in a matched cohort of patients treated with oxaliplatin plus fluoropyrimidines was 3.44 months ( p = 0.007). Between these two groups the median OS of patients with CA 19-9 levels above the statistical median (⩾772.8 kU/l) differed significantly (9.33 versus 6.18 months, p = 0.038). Conclusion: Our data confirms the effectiveness of nal-IRI plus 5-FU/LV treatment as a well-tolerated regimen in the treatment of advanced PAC and extends available data on its use as a second-line treatment option when compared with oxaliplatin plus fluoropyrimidines.
Management of patients eligible for proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors: economic impact and reform proposals
Authors: Jommi Claudio , Cavazza Marianna 
Published: July 2019

Background: PCSK9 inhibitors are indicated for primary hypercholesterolemia (heterozygous familial and non-familial) and for homozygous familial hypercholesterolemia (only evolocumab). They are subject to a drug registry for patient eligibility and follow-up. Patient access to PCSK9 inhibitors is still very limited and varies across regions. Aim: This paper aimed to investigate the cost of the PCSK9-treated patient pathway and main barriers to patient access to medicines and to suggest some changes to this pathway. Methods: The research was conducted through a literature review and an expert panel, which was surveyed through a Delphi approach. The panel included seven clinicians and five pharmacists. Results: If patients are exempt from co-payment, the Italian National Health Service spends €169.70 and €276.93 per year to manage the PCSK9-treated patient pathway, depending on registry coverage (six or three treatment months, respectively). Non-exempt patients pay €176,43 and €271.53 (for six and three months of coverage, respectively) per year. The referral process and the length of the pre-PCSK9 treatment period were considered the main barriers to access. The panelists suggested that the pre-PCSK9 treatment period be shortened to three months; they recommended six months of registry coverage, thereby decreasing the costs compared to three months’ coverage; and they advised that outpatient specialists also be authorized to manage the follow-up. These actions may reduce pathway costs and enhance awareness of the disease. Discussion: The study shows that the pathway of patients eligible for PCSK9 inhibitors can be improved. The surveyed experts integrated pathway-specific recommendations with broader advice to increase awareness on hypercholesterolemia in both citizens and general practitioners.
Surgical treatment of chondroblastoma using extended intralesional curettage with phenol as a local adjuvant
Authors: Zekry Karem M , Yamamoto Norio , Hayashi Katsuhiro , Takeuchi Akihiko , Araki Yoshihiro , Alkhooly Ali Zein AA , Abd-Elfattah Ahmed Saleh , Fouly Ezzat H , Elsaid Ahmed Nady Saleh , Tsuchiya Hiroyuki 
Published: July 2019

Purpose: The aim of this study is to report the clinical and radiological outcomes following surgical treatment of chondroblastoma by means of an extended intralesional curettage using high-speed burr, with phenol as a local adjuvant which is followed by the implantation of synthetic bone graft, aiming to lower the recurrence rate of this tumor. Patients and Methods: This retrospective study included 20 patients with chondroblastoma lesions during the period between 2000 and 2015. Results: Fifteen males and five females were followed up for a mean of 63.35 (26–144) months with average age at the time of presentation was 20.8 (range: 12–32) years. Nineteen patients (95%) were complaining of pain at the time of presentation, and the lesion was discovered accidently in one patient. The mean operative time was 138.5 min (75–250). At the most recent follow-up, all patients had regained full physical function without pain at the operation site. Conclusion: The aggressive treatment of chondroblastoma by an extended intralesional curettage using high-speed burr with phenol as a local adjuvant seems effective in lowering the incidence of local recurrence and secondary more aggressive surgeries. Implantation of the bone defects that result from curettage with the synthetic bone substitutes is a good alternative due to rapid restoration of the mechanical strength with good remodeling.
Knee Extension Does Not Reliably Reduce Acute Type II Tibial Spine Fractures: MRI Evaluation of Displacement During Extension Versus Resting Flexion
Authors: Cannamela Peter C. , Quinlan Noah J. , Maak Travis G. , Adeyemi Temitope F. , Aoki Stephen K. 
Published: July 2019

Background: Type II tibial spine avulsion (TSA) fractures have traditionally been managed by first attempting to achieve closed reduction with extension and immobilization, with surgical indications reserved for those who fail to reduce within 3 mm. However, the frequency with which appropriate reduction can be achieved is largely unknown. Purpose: To evaluate changes in displacement of type II TSA fractures by comparing magnetic resonance imaging (MRI) scans obtained with the knee in flexion and in extension. Study Design: Case series; Level of evidence, 4. Methods: Ten patients with type II TSA fractures were identified. Fracture displacement was measured using 3 images for each patient: (1) initial lateral view radiography, (2) sagittal-plane MRI of the knee in resting flexion, and (3) sagittal-plane MRI of the knee in passive extension. Maximum displacement of the bony fragment was measured in the 2 MRI studies for all patients, and the corresponding change in displacement was calculated. Displacement in flexion was compared with displacement in extension using a paired-sample t test. Statistical significance was set at P < .05. Results: The displacement distance of the bony fragment was reduced by a mean of 0.97 mm on MRI when the knee was in extension compared with flexion in patients with type II TSA fractures ( P = .02). Mean displacement with extension was 6.14 mm, with no fractures reduced below 4 mm. The largest reduction observed was 2.80 mm. The displacement distance increased in 2 knees with extension. The intermeniscal ligament (IML) was entrapped in 4 of 10 patients; however, the amount of reduction achieved did not differ based on the presence of IML entrapment ( P = .85). Conclusion: While the amount of tibial spine displacement warranting surgical treatment can be debated, the study findings suggest that knee extension is not reliable in obtaining adequate closed reduction for type II TSA fractures. Management decisions may need to be based on the initial displacement distance of the fracture, with a lower threshold for operative treatment than previously recognized.
Associations of P2RX7 Functional Diplotypes with Localized Aggressive Periodontitis
Authors: Harris T.H. , Wallace M.R. , Huang H. , Li H. , Shaddox L.M. 
Published: July 2019

Aim: The purpose of this study was to test for the role of the P2X7 receptor in localized aggressive periodontitis (LAP). Methods: Peripheral blood was obtained from 95 subjects with LAP and 76 healthy unrelated controls (HUCs). Three P2RX7 single-nucleotide polymorphisms (rs1718119, rs2230911, and rs3751143) were genotyped from these subjects, and their peripheral blood samples were stimulated with lipopolysaccharide (LPS) from Escherichia coli and tested for inflammatory markers. The 3 P2RX7 single-nucleotide polymorphisms were in found to be in perfect linkage disequilibrium, and a total of 4 haplotypes and 9 diplotypes were identified among all subjects. For both subject populations, the 9 diplotypes were grouped into 4 functional groups and tested for association with subject inflammatory response. To specifically study the effects of extrinsic activation of the P2X7 receptor in LAP, peripheral blood samples from were stimulated under 3 treatments: LPS, LPS + ATP, and LPS +ATP+ P2X7 selective inhibitor. The effects of these treatments on P2X7 receptor activity were measured through Luminex protein assay. Last, to test whether receptor stimulation was related to P2RX7 expression, relative mRNA levels of P2RX7 were quantified with real-time quantitative polymerase chain reaction. Results: Several associations between the P2RX7 diplotypes and LPS-stimulated blood chemokine/cytokine levels were found between the LAP and HUC populations (P < 0.05). P2X7 activation resulted in statistically significant differences in IL-1β and IL-12p40 concentrations for both subject populations. The relative P2RX7 mRNA levels increased significantly after addition of its inhibitor for both LAP and HUC populations. Conclusions: This study detected an association between P2RX7 functional diplotypes and in vitro immune response of whole blood from subjects with LAP. In addition, we found that inhibition of the activated P2X7 receptor leads to increased P2RX7 mRNA levels, suggesting a feedback loop ( ClinicalTrials.gov NCT01330719). Knowledge Transfer Statement: The results of this study suggest that P2RX7 functional diplotypes are associated with LAP and their in vitro immune response to bacteria. Ongoing studies to uncover the mechanistic link between P2RX7 and LAP phenotypes could lead to the development of preventive approaches for susceptible subjects.
Increase in circulating ACE-positive endothelial microparticles during acute lung injury
Authors: Takei Yusuke , Yamada Mitsuhiro , Saito Koji , Kameyama Yoshinobu , Sugiura Hisatoshi , Makiguchi Tomonori , Fujino Naoya , Koarai Akira , Toyama Hiroaki , Saito Kazutomo , Ejima Yutaka , Kawazoe Yu , Kudo Daisuke , Kushimoto Shigeki , Yamauchi Masanori , Ichinose Masakazu 
Published: July 2019

Circulating endothelial microparticles (EMPs) are considered to be markers of endothelial injury, and lung microvascular endothelial cells express higher levels of angiotensin-converting enzyme (ACE). The aim of this study is to examine whether the number of ACE+microvascular EMPs could be a prognostic marker for the development of acute respiratory distress syndrome (ARDS) in septic patients.The numbers of EMPs and ACE+EMPs in the culture supernatant from human microvascular endothelial cells, as well as in the blood of mouse lung injury models and septic patients (n=82), were examined using flow cytometry.ACE+EMPs in the culture supernatant from pulmonary microvascular endothelial cells increased after exposure to an inflammatory stimulus. In the mouse lung injury models, the circulating ACE+EMPs and ACE+EMP/EMP ratio were higher than in the controls (p<0.001). The ACE+EMP/EMP ratio was correlated with the wet/dry lung ratio (rs=0.775, p<0.001). The circulating ACE+EMPs and ACE+EMP/EMP ratio on admission were significantly increased in septic patients who developed ARDS compared with septic patients who did not (p<0.001).Therefore, circulating ACE+EMPs may be a prognostic marker for the development of ARDS in the septic patients.
Defective bacterial phagocytosis is associated with dysfunctional mitochondria in COPD macrophages
Authors: Belchamber Kylie B.R. , Singh Richa , Batista Craig M. , Whyte Moira K. , Dockrell David H. , Kilty Iain , Robinson Matthew J. , Wedzicha Jadwiga A. , Barnes Peter J. , Donnelly Louise E. 
Published: July 2019

Increased reactive oxygen species (ROS) have been implicated in the pathophysiology of chronic obstructive pulmonary disease (COPD). This study examined the effect of exogenous and endogenous oxidative stress on macrophage phagocytosis in patients with COPD.Monocyte-derived macrophages (MDMs) were generated from non-smoker, smoker and COPD subjects, differentiated in either granulocyte macrophage-colony stimulating factor (G-Mφ) or macrophage-colony stimulating factor (M-Mφ). Alveolar macrophages were isolated from lung tissue or bronchoalveolar lavage fluid. Macrophages were incubated in ±200 µM H2O2for 24 h, then exposed to fluorescently labelledHaemophilus influenzaeorStreptococcus pneumoniaefor 4 h, after which phagocytosis, mitochondrial ROS (mROS) and mitochondrial membrane potential (ΔΨm) were measured.Phagocytosis of bacteria was significantly decreased in both G-Mφ and M-Mφ from COPD patients compared with from non-smoker controls. In non-smokers and smokers, bacterial phagocytosis did not alter mROS or ΔΨm; however, in COPD, phagocytosis increased early mROS and decreased ΔΨm in both G-Mφ and M-Mφ. Exogenous oxidative stress reduced phagocytosis in non-smoker and COPD alveolar macrophages and non-smoker MDMs, associated with reduced mROS production.COPD macrophages show defective phagocytosis, which is associated with altered mitochondrial function and an inability to regulate mROS production. Targeting mitochondrial dysfunction may restore the phagocytic defect in COPD.
Painting the Palace of Apries II: ancient pigments of the reliefs from the Palace of Apries, Lower Egypt
Authors: Hedegaard Signe Buccarella , Delbey Thomas , Brøns Cecilie , Rasmussen Kaare Lund 
Published: July 2019

Abstract
Fragments of painted limestone reliefs from the Palace of Apries in Upper Egypt excavated by Flinders Petrie in 1908–1910 have been investigated using visible-induced luminescence imaging, micro X-ray fluorescence, laser ablation inductively coupled plasma mass spectrometry, micro X-ray powder diffraction, and Fourier transform infrared spectrometry. The pigments have been mapped, and the use and previous reports of use of pigments are discussed. Mainly lead–antimonate yellow, lead–tin yellow, orpiment, atacamite, gypsum/anhydrite, and Egyptian blue have been detected. It is the first time that lead–antimonate yellow and lead–tin yellow have been identified in ancient Egyptian painting. In fact, this is the earliest examples known of both of these yellow pigments in the world.
Effects of fish caudal fin sweep angle and kinematics on thrust production during low-speed thunniform swimming
Authors: Matta Alexander , Bayandor Javid , Battaglia Francine , Pendar Hodjat 
Published: July 2019

ABSTRACTScombrid fish lunate caudal fins are characterized by a wide range of sweep angles. Scombrid that have small sweep-angle caudal fins move at higher swimming speeds, suggesting that smaller angles produce more thrust. Furthermore, scombrids occasionally use high angles of attack (AoA) suggesting this also has some thrust benefit. This work examined the hypothesis that a smaller sweep angle and higher AoA improved thrust in swimmers by experimentally analyzing a robophysical model. The robophysical model was tested in a water tunnel at speeds between 0.35 and 0.7 body lengths per second. Three swept caudal fins were analyzed at three different AoA, three different freestream velocities, and four different Strouhal numbers, for a total of 108 cases. Results demonstrated that the fin with the largest sweep angle of 50° resulted in lower thrust production than the 40° and 30° fins, especially at higher Strouhal numbers. Larger AoA up to 25° increased thrust production at the higher Strouhal numbers, but at lower Strouhal numbers, produced less thrust. Differences in thrust production due to fin sweep angle and AoA were attributed to the variation in spanwise flow and leading edge vortex dynamics.
Emerging diverse roles of telocytes
Authors: Kondo Ayano , Kaestner Klaus H. 
Published: July 2019

ABSTRACT
Since the first description of ‘interstitial cells of Cajal’ in the mammalian gut in 1911, scientists have found structurally similar cells, now termed telocytes, in numerous tissues throughout the body. These cells have recently sparked renewed interest, facilitated through the development of a molecular handle to genetically manipulate their function in tissue homeostasis and disease. In this Primer, we discuss the discovery of telocytes, their physical properties, distribution and function, focusing on recent developments in the functional analysis of Foxl1-positive telocytes in the intestinal stem cell niche, and, finally, the current challenges of studying telocytes as a distinct cell type.
The simultaneous interaction of MSL2 with CLAMP and DNA provides redundancy in the initiation of dosage compensation in Drosophila males
Authors: Tikhonova Evgeniya , Fedotova Anna , Bonchuk Artem , Mogila Vladic , Larschan Erica N. , Georgiev Pavel , Maksimenko Oksana 
Published: July 2019

ABSTRACT
The binding of the Drosophila male-specific lethal dosage compensation complex (DCC) exclusively to the male X chromosome provides an excellent model system to understand mechanisms of selective recruitment of protein complexes to chromatin. Previous studies showed that the male-specific organizer of the complex, MSL2, and the ubiquitous DNA-binding protein CLAMP are key players in the specificity of X chromosome binding. The CXC domain of MSL2 binds to genomic sites of DCC recruitment in vitro. Another conserved domain of MSL2, named Clamp-binding domain (CBD) directly interacts with the N-terminal zinc-finger domain of CLAMP. Here, we found that inactivation of CBD or CXC individually only modestly affected recruitment of the DCC to the X chromosome in males. However, combination of these two genetic lesions within the same MSL2 mutant resulted in an increased loss of DCC recruitment to the X chromosome. Thus, proper MSL2 positioning requires an interaction with either CLAMP or DNA to initiate dosage compensation in Drosophila males.