bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mast cell–induced immunopathology in recurrent pregnancy losses
Authors: Derbala Youssef , Elazzamy Haidy , Bilal Mahmood , Reed Rachel , Salazar Garcia Maria Dinorah , Skariah Annie , Dambaeva Svetlana , Fernandez Emilio , Germain Alfredo , Gilman‐Sachs Alice , Beaman Kenneth , Kwak‐Kim Joanne 
Published: April 2019

AbstractProblemMast cells (MC) have been known to play an important role in inflammation and angiogenesis by secreting numerous mediators, such as proteases, gelatinases, and proteoglycans. Three different MC subtypes were found in the endometrial layers of the uterus. In this study, we aim to investigate the role of endometrial MCs in recurrent pregnancy losses (RPL).Method of studyEndometrial biopsy was performed 5‐7 days post‐ovulation (implantation window) in women with a history of two or more RPL (n = 46) and normal fertile women (n = 10). Quantitative RT‐PCR was performed to detect the expression of various mast cell mediators. Endometrial samples were evaluated using immunohistochemistry for c‐kit receptor (CD117) and tryptase (MC activation marker).ResultsMast cells were present throughout the entire layers of the endometrium; their count was elevated in RPL patients as compared to controls. The gene expression of c‐Kit receptor was not different between the study groups. There are significant increases in the mRNA expression of various mediators, that is, stem cell factor (P = 0.029), tryptase (P = 0.024), heparan sulfate (P = 0.0005), and MMP‐2 (P < 0.0001) in women with RPL as compared to normal controls. Chymase gene expression was not detected in most of the endometrial samples.ConclusionThis study has shown that MCs are overactive in RPL patients by creating a pro‐inflammatory milieu, suggesting a novel role in the immunopathology of RPL. Future studies are needed to better understand the role of MC in implantation and placental angiogenesis.
Relating glaucomatous visual field loss to retinal oxygen delivery and metabolism
Authors: Aref Ahmad A , Maleki Shervin , Tan Ou , Huang David , Varma Rohit , Shahidi Mahnaz 
Published: April 2019

AbstractPurposeTo test the hypothesis that visual field (VF) loss is associated with decreased retinal blood flow, oxygen delivery and metabolism, and with increased retinal oxygen extraction fraction (OEF) in glaucomatous individuals.MethodsGlaucomatous subjects underwent automated perimetry, dual wavelength scanning laser ophthalmoscopy and Doppler optical coherence tomography imaging in order to measure mean deviation, central retinal arterial and venous diameter equivalents (CRAE and CRVE), oxygen saturation levels and total retinal blood flow (TRBF), respectively. Retinal oxygen delivery, metabolism and extraction fraction were derived from measurements of oxygen saturation and blood flow.ResultsTwenty eyes of 14 subjects were included in the study. Mean deviation was on average −13.76 ± 8.70 dB. Mean CRAE and CRVE were 126 ± 28 and 191 ± 35 μm, respectively. Mean TRBF and oxygen delivery were 34.3 ± 11.7 μl/min and 6.5 ± 2.6 μl O2/min, respectively. Mean oxygen metabolism and extraction fraction were 2.1 ± 0.94 μl O2/min and 0.34 ± 0.15, respectively. Visual field (VF) loss was associated with reduced CRAE and CRVE, TRBF and oxygen delivery and associated with increased OEF.ConclusionCombined measurements of retinal blood flow and oxygen saturation in glaucomatous individuals suggest VF loss is associated with impaired oxygen delivery and augmented OEF.
The Swedish Neonatal Quality Register – contents, completeness and validity
Authors: Norman Mikael , Källén Karin , Wahlström Erik , Håkansson Stellan ,   The SNQ Collaboration
Published: April 2019

AbstractAimTo describe the Swedish Neonatal Quality Register (SNQ) and to determine its completeness and agreement with other registers.MethodsSNQ collects data for infants admitted to neonatal units during the first four postnatal weeks. Completeness and registers’ agreement were determined cross‐linking SNQ data with Swedish population registers (the Inpatient, Medical Birth and Cause of Death Registers) for a study period of five years.ResultsIn total, 84 712 infants were hospitalised. A total of 52 806 infants occurred in both SNQ and the population registers; 28 692 were only found in the population registers, and 3214 infants were only found in SNQ. Between gestational weeks 24–34, completeness of SNQ was 98–99%. Below and above these gestational ages, completeness was lower. Infants missing in SNQ were term or near‐term in 99% of the cases, and their diagnoses indicated conditions managed in maternity units, or re‐admissions for acute infections, managed in paediatric units. For most diagnoses, the agreement between SNQ and population registers was high, but some (bronchopulmonary dysplasia and grade of hypoxic‐ischaemic encephalopathy) were often missing in the population registers.ConclusionSNQ completeness and agreement against other registers, especially for preterm infants, is excellent. SNQ is a valid tool for benchmarking, quality improvement and research.
Urokinase‐type plasminogen activator (uPA) is not essential for epithelial sodium channel (ENaC)‐mediated sodium retention in experimental nephrotic syndrome
Authors: Bohnert Bernhard N. , Daiminger Sophie , Wörn Matthias , Sure Florian , Staudner Tobias , Ilyaskin Alexandr V. , Batbouta Firas , Janessa Andrea , Schneider Jonas C. , Essigke Daniel , Kanse Sandip , Haerteis Silke , Korbmacher Christoph , Artunc Ferruh 
Published: April 2019

AbstractAimIn nephrotic syndrome, aberrantly filtered plasminogen (plg) is converted to active plasmin by tubular urokinase‐type plasminogen activator (uPA) and thought to lead to sodium retention by proteolytic activation of the epithelial sodium channel (ENaC). This concept predicts that uPA is an important factor for sodium retention and that inhibition of uPA might be protective in nephrotic syndrome.MethodsActivation of amiloride‐sensitive currents by uPA and plg were studied in Xenopus laevis oocytes expressing murine ENaC. In doxorubicin‐induced nephrotic mice, uPA was inhibited pharmacologically by amiloride and genetically by the use of uPA‐deficient mice (uPA−/−).ResultsExperiments in Xenopus laevis oocytes expressing murine ENaC confirmed proteolytic ENaC activation by a combination of plg and uPA which stimulated amiloride‐sensitive currents with concomitant cleavage of the ENaC γ‐subunit at the cell surface. Treatment of nephrotic wild‐type mice with amiloride inhibited urinary uPA activity, prevented urinary plasmin formation and sodium retention. In nephrotic mice lacking uPA (uPA−/−), urinary plasmin formation from plg was suppressed and urinary uPA activity absent. However, in nephrotic uPA−/− mice, sodium retention was not reduced compared to nephrotic uPA+/+ mice. Amiloride prevented sodium retention in nephrotic uPA−/− mice which confirmed the critical role of ENaC in sodium retention.ConclusionuPA is responsible for the conversion of aberrantly filtered plasminogen to plasmin in the tubular lumen in vivo. However, uPA‐dependent plasmin generation is not essential for ENaC‐mediated sodium retention in experimental nephrotic syndrome.
Asylum‐Seeking Work, Precariousness, and the Making of Claimant‐Workers
Authors: Shrestha Tina 
Published: April 2019

AbstractThis article contributes to the anthropological discussion on precariousness and labor precarity, with regard to temporality, potentiality, and subjectivity, by examining how asylum‐seeking accounts intersect with, interrupt, and, above all, inform people's everyday labor activities outside the asylum process. Drawing on my ethnographic research among Nepali migrants and asylum seekers in the United States, I document people's adoption of a familiar sociocultural understanding of “the work of making paper” and retrospective logic to describe their subjective entanglement with the asylum documentation process and their impending labor subordination. I argue that it is through asylum‐seeking work that people participate in and inhabit the precarization process, sustaining and exacerbating, in some cases, their precarious working lives. In this sense, asylum‐seeking work involves a subjective transformation of asylum seekers into precarious “claimant‐workers,” providing the condition of possibility for labor precariousness.
Histopathological evidence for macrophage activation driving post‐transfusion hyperhaemolysis syndrome
Authors: Win Nay , Lucas Sebastian , Hebballi Sangam , McKernan Angela , Hamilton Rosie , Robinson Ivan , Chen Frederick 
Published: April 2019

SummaryPost‐transfusion hyperhaemolysis syndrome (PTHS) is a rare life‐threatening transfusion complication reported mainly in sickle cell patients. Its pathogenesis is poorly understood. Antibody‐mediated haemolysis and bystander effect have been proposed as putative mechanisms, but in half of cases, red cell antibodies are undetectable, and PTHS develops despite transfusion of cross‐matched compatible RBC. An alternate hypothesis proposes activated macrophages as the main drivers of red cell destruction through direct phagocytosis. We report the histopathological findings of two patients with PTHS showing extensive macrophage expansion and erythrophagocytosis, supportive of macrophage activation driving PTHS. This supports a possible role for novel therapies that target macrophage activation.
Phosphorylated NUB1 distinguishes α‐synuclein in Lewy bodies from that in glial cytoplasmic inclusions in multiple system atrophy
Authors: Tanji Kunikazu , Miki Yasuo , Mori Fumiaki , Kon Tomoya , Kakita Akiyoshi , Takahashi Hitoshi , Wakabayashi Koichi 
Published: April 2019

AbstractPosttranslational modifications by phosphorylation, ubiquitination, neddylation and other pathways have emerged as major regulators of cellular functions. NEDD8 ultimate buster 1, NUB1, is an adaptor protein, which negatively regulates the levels of the ubiquitin‐like protein NEDD8 as well as neddylated proteins through proteasomal degradation. We previously reported that NUB1 is highly involved in the pathogenesis of synucleinopathy including Parkinson's disease (PD), dementia with Lewy bodies (DLB) and multiple system atrophy (MSA). In general, since phosphorylation is strongly related to the alteration of protein propensity, we examined if the fundamental function of NUB1 can be modulated by its phosphorylation. We created a series of phosphomimic mutants of NUB1. Among them, we found that phosphorylation of NUB1 at S46 (P‐NUB46) efficiently degrades aggregates using a cell‐based assay. Immunohistochemical studies have shown that specific antibodies against P‐NUB46 reacted with Lewy bodies in PD and DLB but not with glial cytoplasmic inclusions in MSA. Moreover, P‐NUB46 levels were significantly higher in the brains of patients with DLB than in control brains, and P‐NUB46 was extracted in an insoluble fraction of DLB. These findings suggest that the phosphorylation of NUB1 is modulated during the pathological process of Lewy body disease.
Increasing earnings inequality and the gender pay gap in Canada: Prospects for convergence
Authors: Fortin Nicole M. 
Published: April 2019

AbstractThis paper retraces the evolution of Canadian women's labour force participation and of the gender earnings ratio across the generations to understand better the prospects for gender convergence in pay. Using data from the public use Labour Force Surveys (LFS) and administrative annual earnings data from the Longitudinal Worker Files (LWF), the paper assesses the role of increasing top earnings inequality in the persistence of the gender pay gap. Having identified a growing role for the under‐representation of women among top earners, the paper then performs an evaluation and critical analysis of existing gender equality policies, centred on horizontal occupational gender segregation, and discusses alternative policies for the future.
MicroRNA‐204‐5p: A novel candidate urinary biomarker of Xp11.2 translocation renal cell carcinoma
Authors: Kurahashi Ryoma , Kadomatsu Tsuyoshi , Baba Masaya , Hara Chiaki , Itoh Hitoshi , Miyata Keishi , Endo Motoyoshi , Morinaga Jun , Terada Kazutoyo , Araki Kimi , Eto Masatoshi , Schmidt Laura S. , Kamba Tomomi , Linehan W. Marston , Oike Yuichi 
Published: April 2019

AbstractXp11.2 translocation renal cell carcinoma (Xp11 tRCC) is a rare sporadic pediatric kidney cancer caused by constitutively active TFE3 fusion proteins. Tumors in patients with Xp11 tRCC tend to recur and undergo frequent metastasis, in part due to lack of methods available to detect early‐stage disease. Here we generated transgenic (Tg) mice overexpressing the human PRCC‐TFE3 fusion gene in renal tubular epithelial cells, as an Xp11 tRCC mouse model. At 20 weeks of age, mice showed no histological abnormalities in kidney but by 40 weeks showed Xp11 tRCC development and related morphological and histological changes. MicroRNA (miR)‐204‐5p levels in urinary exosomes of 40‐week‐old Tg mice showing tRCC were significantly elevated compared with levels in control mice. MicroRNA‐204‐5p expression also significantly increased in primary renal cell carcinoma cell lines established both from Tg mouse tumors and from tumor tissue from 2 Xp11 tRCC patients. All of these lines secreted miR‐204‐5p‐containing exosomes. Notably, we also observed increased miR‐204‐5p levels in urinary exosomes in 20‐week‐old renal PRCC‐TFE3 Tg mice prior to tRCC development, and those levels were equivalent to those in 40‐week‐old Tg mice, suggesting that miR‐204‐5p increases follow expression of constitutively active TFE3 fusion proteins in renal tubular epithelial cells prior to overt tRCC development. Finally, we confirmed that miR‐204‐5p expression significantly increases in noncancerous human kidney cells after overexpression of a PRCC‐TFE3 fusion gene. These findings suggest that miR‐204‐5p in urinary exosomes could be a useful biomarker for early diagnosis of patients with Xp11 tRCC.
Improving glucocorticoid replacement profiles in adrenal insufficiency
Authors: Choudhury Sirazum , Lightman Stafford , Meeran Karim 
Published: April 2019

AbstractThere is an increased mortality associated with adrenal insufficiency despite glucocorticoid replacement therapy with a standardized mortality ratio greater than two. The cause of the increased mortality is yet to be definitively elucidated, but may be due to excess steroid exposure, or replacement regimens that are uncoupled from the normal physiological cortisol profile. Cortisol secretion follows an ultradian pattern which is not possible to reproduce using oral replacement. With the advent of new pumps, it is now possible to mimic the pulsatility of the adrenal glands. While the cognitive and emotional benefits of reproducing the ultradian rhythm are known, the presence of long‐term benefits is not yet clear. There is a dearth of evidence and high‐quality studies to underline our current understanding of the pathophysiology of adrenal insufficiency and replacement therapy. There is a particular lack of research comparing objective outcomes between patients receiving hydrocortisone replacement (either standard therapy or new sustained release preparations), prednisolone replacement and ultradian pumps. Direct comparative studies are now warranted to understand the optimal approach.
Influence of implant neck and abutment characteristics on peri‐implant tissue health and stability. Oral reconstruction foundation consensus report
Authors: Schwarz Frank , Messias Ana , Sanz‐Sánchez Ignacio , Carrillo de Albornoz Ana , Nicolau Pedro , Taylor Tom , Beuer Florian , Schär Alex , Sader Robert , Guerra Fernando , Sanz Mariano 
Published: April 2019

AbstractObjectiveThe aim of this consensus meeting was to assess the influence of implant neck and abutment characteristics on peri‐implant tissue health and stability.Material and MethodsGroup and plenary discussions were based on two systematic reviews focusing on the effect of titanium implants with different collar designs/surface modifications and the abutment material on the stability of marginal bone levels (MBLs), peri‐implant health, and survival rates.ResultsThe changes in MBLs were not influenced by the abutment material and were also similar at one‐ and two‐piece implants after one year of loading. Rough collar implants improved MBLs in comparison to machined collar implants. Additional modifications of the collar had no beneficial clinical effect on MBLs. Titanium abutments were associated with significantly higher increases in bleeding on probing when compared with zirconia abutments.ConclusionMBLs are mainly influenced by the microstructure (i.e., rough surfaced) of the implant neck. Consensus statements and specific recommendations for future research were elaborated during the consensus meeting.
Effect of enamel matrix derivative liquid in combination with a natural bone mineral on new bone formation in a rabbit GBR model
Authors: Kobayashi Eizaburo , Fujioka‐Kobayashi Masako , Saulacic Nikola , Schaller Benoit , Sculean Anton , Miron Richard J. 
Published: April 2019

AbstractObjectivesRecently, a new liquid carrier system for enamel matrix derivate (EMD‐liquid) was developed with better physico‐chemical properties for improved adsorption of EMD to biomaterial surfaces. The aim of the present study was to investigate the bone regenerative potential of EMD‐liquid in combination with a natural bone mineral (NBM) in vivo.MethodsFour 6‐mm defects were created in the calvaria of six New Zealand white rabbits. Defects were filled with either (1) control (empty), (2) 20 mg of NBM, or (3) 20 mg of NBM + 20 µl of EMD‐liquid (n = 8). All defects were covered with collagen barrier membranes. The bone regenerative potential was investigated by micro‐CT and histomorphological analyses at 8 weeks postsurgery.ResultsThe mineralized tissue volume was significantly higher in the NBM + EMD‐liquid group when compared to control, whereas no difference was observed between the NBM alone and control groups. While no significant difference was observed for horizontal bone defect closure between the NBM + EMD‐liquid and the NBM alone groups, NBM + EMD‐liquid significantly increased the total mineralized area and reduced the percentage of soft/connective tissue infiltration. No statistically significant difference was observed between the NBM + EMD‐liquid group and NBM alone group for amount of mineralized bone.ConclusionThe addition of EMD‐liquid did not lead to statistically significant bone formation when compared to NBM alone. The combination of NBM + EMD‐liquid but not NBM alone did however induce superior mineralized tissues when compared to control (empty). Further research investigating the adsorption potential of EMD‐liquid to bone‐grafting particles with/without collagen may provide valuable insights into future regenerative strategies with enamel matrix proteins.
Changes in ventilation and perfusion following lower lobe endoscopic lung volume reduction (ELVR) with endobronchial valves in severe COPD
Authors: Yang Li , Hsu Kelvin , Williamson Jonathan P. , Peters Matthew J. , Ho‐Shon Kevin , Ing Alvin J. 
Published: April 2019

AbstractBackgroundWe have previously reported significant improvements in ventilation and perfusion (VQ) and V/Q matching in the contralateral lung, especially the non‐targeted lower zone in patients with severe COPD following upper lobe ELVR with endobronchial valves. However, V/Q changes after lower lobe ELVR have not been described.MethodsSeven patients with lower lobe heterogeneous emphysema underwent unilateral lower lobe ELVR at Macquarie University Hospital. Lung function tests, 6‐minute walk tests (6MWT), St George’s Respiratory Questionnaire (SGRQ) and planar differential VQ scans were performed at baseline and at 1, 3 and 12 months post‐ELVR.ResultsCompared to baseline, patients showed significant improvements in FEV1 (0.83 ± 0.09L‐0.97 ± 0.12L, p < 0.05), 6MWD (200.33 ± 56.54 m‐274.24 ± 48.03 m, p < 0.05) and SGRQ (61.13 ± 5.33‐42.86 ± 6.99, p < 0.05) at 3 months after ELVR. This improvement was maintained at 12 months. There was a corresponding significant improvement in the differential ventilation (30.21 ± 3.04%‐37.82 ± 3.76%, p < 0.05) and perfusion (31.77 ± 2.53%‐35.60 ± 2.58%, p < 0.05) of the contralateral non‐targeted upper zone.ConclusionsWithin the limitations of a small sample size, we have found that in heterogeneous severe COPD patients undergoing ELVR targeting the lower lobes, there are clinical and PFT improvements similar to that reported in ELVR targeting upper lobes. Contralateral improvement in V/Q matching also occurs following lower lobe ELVR with the greatest improvement in the contralateral upper zone, suggesting the contralateral upper lobe should be the least affected lobe if the lower lobe is targeted in ELVR. These findings need to be confirmed in a study with a larger number of patients.
Corticosteroids and methotrexate as adjuvants to costimulation blockade in non‐human primate renal transplantation
Authors: Anderson Douglas J. , Lo Denise J. , Leopardi Francis , Song Mingqing , Strobert Elizabeth A. , Jenkins Joe B. , Larsen Christian P. , Kirk Allan D. 
Published: April 2019

AbstractBelatacept, the CD28‐B7 costimulation pathway inhibitor, has been approved as a calcineurin inhibitor (CNI) alternative in kidney transplantation. Although costimulation blockade (CoB) allows for CNI avoidance, it is associated with increased rates of early rejection, prompting a search for agents to pair with belatacept. Methotrexate (MTX) is an antimetabolite that has been found to be complimentary with abatacept, a lower affinity CD28‐B7‐specific analogue of belatacept, in the treatment of rheumatoid arthritis (RA). We examined whether this synergy would extend to prevention of kidney allograft rejection. Rhesus macaques underwent kidney transplantation treated with abatacept maintenance therapy with either a steroid taper, MTX, or both. The combination of abatacept maintenance with steroids prolonged graft survival compared to untreated historical controls and previous reports of abatacept monotherapy. The addition of MTX did not provide additional benefit. These data demonstrate that abatacept with adjuvant therapy may delay the onset of acute rejection, but fail to show synergy between abatacept and MTX beyond that of steroids. These findings indicate that MTX is unlikely to be a suitable adjuvant to CoB in kidney transplantation, but also suggest that with further modification, a CoB regimen used for advanced RA may suffice for RA patients requiring kidney transplantation.