bluuebunny/crossref_metadata_2025_split huggingface dataset:
MiR‐101a ameliorates AngII‐mediated hypertensive nephropathy by blockade of TGFβ/Smad3 and NF‐κB signalling in a mouse model of hypertension
Authors: Ding Hong , Zhou Ying , Huang Haihua 
Published: October 2018

SummaryHypertensive nephropathy, clinically characterized by progressive renal fibrosis and inflammation, is a severe complication of hypertension. The objectives of this study were to investigate the roles of miR‐101a in relieving angiotensin II (Ang II)‐mediated hypertensive nephropathy and uncover the possible underlying mechanisms. A hypertensive mouse model was established via continuous 28‐day AngII infusion. Systolic blood pressure (SBP), ratio of urine albumin to creatinine, blood urea nitrogen (BUN), serum creatinine (Scr) and glomerular filtration rate (GFR) were evaluated. Dual luciferase reporter assay was used to explore the target of miR‐101a. mRNA levels of miR‐101a, TGFβRI, fibrotic markers (Collagen I and α‐SMA) and pro‐inflammatory cytokines (IL‐1β and TNF‐α) were determined by real‐time PCR. Protein levels of TGFβRI, Collagen I, α‐SMA, IL‐1β, TNF‐α, t‐p65, P‐p65, t‐Smad3, P‐Smad3, t‐IκBα and P‐IκBα were detected by western blot. MiR‐101a mimics significantly improved GFR and inhibited AngII‐induced increase in the ratio of urine albumin to creatinine, BUN and Scr. MiR‐101a mimics partially abolished AngII‐induced increase in the mRNA and protein level of fibrotic markers by targeting TGFβRI and inhibiting TGFβ/Smad3 pathway. Moreover, TGFβRI inhibitor galunisertib inhibited AngII‐mediated renal injury in mice with hypertensive nephropathy. Additionally, miR‐101a overexpression blocked AngII‐induced up‐regulation of pro‐inflammatory markers via suppressing NF‐κB pathway. MiR‐101a exhibited protective effects against hypertensive nephropathy via inhibiting TGFβ/Smad3 and NF‐κB signalling pathways.
When knowledgeable neighbors also share seedlings: diffusion of banana cultivation in Tanzania
Authors: Larsen Anna Folke 
Published: October 2018

AbstractNetworks have been found to increase adoption of technology by providing information about the new technology (e.g., Conley and Udry, 2010). However, little is known about provision of necessary inputs for adoption through networks. Using data from an intervention in Tanzania, I discuss how a farmer's network can also affect the adoption of improved banana cultivation by providing seedlings. A solidarity chain principle obliged project farmers to pass on improved seedlings to other farmers free of charge. I provide a theoretical framework to guide intuition for the empirical results and suggest an empirical distinction between information and input provision through networks. Empirically, I find support for network effects through provision of both information and inputs, jointly boosting the network effect on adoption: a farmer is 39 percentage points more likely to adopt banana cultivation if there is at least one banana grower in the farmer's network compared to none. In this setting, it is not possible to fully disentangle the input and information channel. While the findings suggest that a solidarity chain principle could be an interesting avenue to boost local diffusion of new technologies, more research is needed to unpack the causal impact and the interplay with existing input markets.
The steadily growing problem of lentigo maligna and lentigo maligna melanoma in Australia: Population‐based data on diagnosis and management
Authors: Guitera Pascale , Collgros Helena , Madronio Christine M , Goumas Christopher , Mann Graham J , Watts Caroline G , Pereira Amanda R , Armstrong Bruce K , Drummond Martin , Morton Rachael L , Scolyer Richard A , Menzies Scott W , Thompson John F , Cust Anne E 
Published: October 2018

AbstractBackground/ObjectivesThere are limited population‐based data documenting the incidence and management of lentigo maligna (LM) and invasive lentigo maligna melanoma (LMM). We report the data on occurrence and management of LM and LMM in an Australian population.MethodsProspective collection of incidence and clinician‐reported management of melanoma in situ (MIS; n = 450, capped) and localised invasive melanoma (n = 3251) notified to the New South Wales Cancer Registry over 12‐months in 2006–2007.ResultsThe estimated annual incidence of all MIS was 27.0 per 100 000 (LM 12.2, non‐LM MIS 5.9 and unclassified MIS 9.0). Patients with LM or LMM were on average approximately 10 years older than those with other melanoma subtypes (P < 0.001). The head and neck was the location of 59% of LM, 44% of LMM and <20% of other melanoma subtypes (P < 0.001). The majority of LM and LMM were treated only by specialists. Diagnostic partial biopsies were more frequent for LM and LMM than for other melanoma subtypes, and primary care physicians were more likely than specialists to do a punch partial biopsy than a shave biopsy. The reported median definitive excision margin for LM was 5.0 mm compared with 7.2 mm for non‐LM MIS (P = 0.001).ConclusionsIn this Australian population, LM was twice as frequent as other types of MIS. Improved strategies for diagnosis and management are required.
Kete pikau: A basket of knowledge – ‘guidelines from back home’
Authors: Koroheke‐Rogers Marara , Blattner Katharina 
Published: October 2018

AbstractFrom the perspective of one rural New Zealand Māori community involved in a health service research study, this article describes ‘Te Tomokanga’ – an established local Māori model of engagement. This model served as an essential guide for researchers coming into the community and at the same time, enabled the community to take ownership of the research process. This may have applicability to research in rural Indigenous communities elsewhere.
Long‐term cost comparison between surgical and medical therapy for benign prostatic hyperplasia: a study using hospital billing data
Authors: Ahn Hyun Soo , Kim Se Joong , Choi Jong Bo , Choo Seol Ho , Shim Kang Hee , Kim Sun Il 
Published: October 2018

ObjectivesTo analyse actual long‐term medical treatment of benign prostatic hyperplasia (BPH) and compare the incurred cost with that of patients with BPH who underwent early surgery.Patients and methodsPatients who were first diagnosed with BPH from 1 January 2008 to 31 December 2010 were identified using the Clinical Data Warehouse. Hospital billing data generated by the electronic hospital management system were collected until December 2015. For outpatient care, only procedures, materials and drugs directly related to the management of BPH were selected for the analysis. For inpatient care, all procedures, materials and drugs ordered on dates with continuity with BPH surgery date were included. The primary endpoint of the study was the total treatment‐related direct costs of patients undergoing a long‐term curative medical therapy for BPH (Group 1), which was arbitrarily defined as any medical therapy including a 5α‐reductase inhibitor with a minimum medication possession ratio of 0.5 during ≥5 consecutive years, or ≥1 year until BPH surgery due to medical therapy failure. In all, 70 patients who underwent BPH surgery at <1 year of initial visit served as controls (Group 2).ResultsAmongst 137 patients in the Group 1, four patients underwent BPH surgery at a median of 57.8 months after the initial visit (2.9%). At a median follow‐up of 76 months, the mean total treatment cost was significantly higher in Group 1 than in Group 2 ($3987 vs $3036 [USA dollars], P < 0.001). Similarly, the mean ‘out‐of‐pocket’ cost was significantly higher in Group 1 than in Group 2 ($1742 vs $1436, P = 0.005). When a linear increment of annual BPH treatment cost is assumed for Group 1 and all costs are assumed to be produced within the first year for Group 2, the total and out‐of‐pocket costs became equal at the end of the fifth year of medical treatment. For both total and out‐of‐pocket costs, medication‐related costs occupied the largest proportion, exceeding half of the costs.ConclusionsWe suggest patient counselling at the beginning of BPH treatment should include the likelihood that the cumulative out‐of‐pocket cost at 5 years of continuous medication will exceed that of early surgery. Our cost study using hospital billing data extractable from the electronic hospital management system may be a good model for cost studies that could provide valuable information to health providers and payers.
Oxidative stress and inflammation in a spectrum of epileptogenic cortical malformations: molecular insights into their interdependence
Authors: Arena Andrea , Zimmer Till S. , van Scheppingen Jackelien , Korotkov Anatoly , Anink Jasper J. , Mühlebner Angelika , Jansen Floor E. , van Hecke Wim , Spliet Wim G. , van Rijen Peter C. , Vezzani Annamaria , Baayen Johannes C. , Idema Sander , Iyer Anand M. , Perluigi Marzia , Mills James D. , van Vliet Erwin A. , Aronica Eleonora 
Published: October 2018

AbstractOxidative stress (OS) occurs in brains of patients with epilepsy and coincides with brain inflammation, and both phenomena contribute to seizure generation in animal models. We investigated whether expression of OS and brain inflammation markers co‐occurred also in resected brain tissue of patients with epileptogenic cortical malformations: hemimegalencephaly (HME), focal cortical dysplasia (FCD) and cortical tubers in tuberous sclerosis complex (TSC). Moreover, we studied molecular mechanisms linking OS and inflammation in an in vitro model of neuronal function. Untangling interdependency and underlying molecular mechanisms might pose new therapeutic strategies for treating patients with drug‐resistant epilepsy of different etiologies. Immunohistochemistry was performed for specific OS markers xCT and iNOS and brain inflammation markers TLR4, COX‐2 and NF‐κB in cortical tissue derived from patients with HME, FCD IIa, IIb and TSC. Additionally, we studied gene expression of these markers using the human neuronal cell line SH‐SY5Y in which OS was induced using H2O2. OS markers were higher in dysmorphic neurons and balloon/giant cells in cortex of patients with FCD IIb or TSC. Expression of OS markers was positively correlated to expression of brain inflammation markers. In vitro, 100 µM, but not 50 µM, of H2O2 increased expression of TLR4, IL‐1β and COX‐2. We found that NF‐κB signaling was activated only upon stimulation with 100 µM H2O2 leading to upregulation of TLR4 signaling and IL‐1β. The NF‐κB inhibitor TPCA‐1 completely reversed this effect. Our results show that OS positively correlates with neuroinflammation and is particularly evident in brain tissue of patients with FCD IIb and TSC. In vitro, NF‐κB is involved in the switch to an inflammatory state after OS. We propose that the extent of OS can predict the neuroinflammatory state of the brain. Additionally, antioxidant treatments may prevent the switch to inflammation in neurons thus targeting multiple epileptogenic processes at once.
Accuracy of grading pancreatic neuroendocrine neoplasms with Ki‐67 index in fine‐needle aspiration cellblock material
Authors: Grosse Claudia , Noack Petar , Silye Rene 
Published: October 2018

ObjectiveThe aim of this study was to assess the preoperative tumour grade of pancreatic neuroendocrine neoplasms (panNENs) by determining the Ki‐67 index in endoscopic ultrasound‐guided fine needle aspiration (EUS‐FNA) material and to correlate the preoperative tumour grade with the postoperative tumour grade in surgical specimens.MethodsWe performed a retrospective review of the institutional pathology database over a 10‐year period (2007‐2017) to identify all cases of panNENs with corresponding preoperative EUS‐FNA cytological material and surgical specimens. Fifteen cases with adequate EUS‐FNA material (more than 400 tumour cells on cellblock) were identified. The cytological and histological samples were graded based on the mitotic rate and the Ki‐67 index in accordance with the 2017 World Health Organisation grading system for panNENs. The tumour grades determined on EUS‐FNA cellblock material were compared with the histological tumour grades.ResultsMean age at diagnosis was 64.8 ± 12.7 years (range, 38‐85 years). The grading scores assigned to the cytological and histological samples were concordant in all 15 (100%) cases. Of those, two (13%) cases were scored as grade 1, nine (60%) cases as grade 2 and four (27%) cases as grade 3 tumours.ConclusionOur study shows that tumour grade in patients with PanNENs can be reliably determined by assessing the Ki‐67 index in EUS‐FNA specimens based on the 2017 World Health Organisation classification and grading system.
Deferasirox in children with transfusion‐dependent thalassemia or sickle cell anemia: A large cohort real‐life experience from Turkey (REACH‐THEM)
Authors: Antmen Bulent , Karakaş Zeynep , Yeşilipek Mehmet Akif , Küpesiz Osman Alphan , Şaşmaz İlgen , Uygun Vedat , Kurtoğlu Erdal , Oktay Gonul , Aydogan Gonul , Akın Mehmet , Salcioglu Zafer , Vergin Canan , Kazancı Elif Güler , Ünal Selma , Çalışkan Ümran , Aral Yusuf Ziya , Türkkan Emine , Meral Güneş Adalet , Tunç Bahattin , Gümrük Fatma , Ayhan Aylin Canbolat , Söker Murat , Koç Ahmet , Oymak Yeşim , Ertem Mehmet , Timur Çetin , Yıldırmak Yıldız , İrken Gülersu , Apak Hilmi , Biner Betül , Eren Tuğba Gürleyen , Işık Balcı Yasemin , Koçak Ülker , Karasu Gülsün , Akkaynak Diyar , Patıroğlu Türkan 
Published: October 2018

AbstractObjectivesTo evaluate the long‐term efficacy and safety of deferasirox therapy in a large observational cohort of children with transfusion‐dependent thalassemia (TDT) and sickle cell anemia (SCA) in Turkey.MethodsThis was a multicenter, prospective cohort study including TDT and SCA patients aged 2‐18 years with iron overload (≥100 mL/kg of pRBC or a serum ferritin [SF] level >1000 μg/L) receiving deferasirox. Patients were followed for up to 3 years according to standard practice.ResultsA total of 439 patients were evaluated (415 [94.5%] TDT, 143 [32.6%] between 2 and 6 years). Serum ferritin levels consistently and significantly decreased across 3 years of deferasirox therapy from a median of 1775.5 to 1250.5 μg/L (P < 0.001). Serum ferritin decreases were noted in TDT (1804.9 to 1241 μg/L), SCA (1655.5 to 1260 μg/L), and across age groups of 2‐6 years (1971.5 to 1499 μg/L), 7‐12 years (1688.5 to 1159.8 μg/L), and 13‐18 years (1496.5 to 1107 μg/L). Serum ferritin decreases were also noted for all deferasirox dose groups but only significant in patients with doses ≥30 mg/kg/d (n = 120, −579.6 median reduction, P < 0.001). Only 9 (2%) patients had adverse events suspected to be related to deferasirox. Serum creatinine slightly increased but remained within the normal range.ConclusionsDeferasirox has long‐term efficacy and safety in children with TDT and SCA, although higher doses (≥30 mg/kg/d) may be required to achieve iron balance.
Biochemical characterization of the minimal domains of an iterative eukaryotic polyketide synthase
Authors: Sabatini Martin , Comba Santiago , Altabe Silvia , Recio‐Balsells Alejandro I. , Labadie Guillermo R. , Takano Eriko , Gramajo Hugo , Arabolaza Ana 
Published: October 2018

Iterative type I polyketide synthases (PKS) are megaenzymes essential to the biosynthesis of an enormously diverse array of bioactive natural products. Each PKS contains minimally three functional domains, β‐ketosynthase (KS), acyltransferase (AT), and acyl carrier protein (ACP), and a subset of reducing domains such as ketoreductase (KR), dehydratase (DH), and enoylreductase (ER). The substrate selection, condensation reactions, and β‐keto processing of the polyketide growing chain are highly controlled in a programmed manner. However, the structural features and mechanistic rules that orchestrate the iterative cycles, processing domains functionality, and chain termination in this kind of megaenzymes are often poorly understood. Here, we present a biochemical and functional characterization of the KS and the AT domains of a PKS from the mallard duck Anas platyrhynchos (ApPKS). ApPKS belongs to an animal PKS family phylogenetically more related to bacterial PKS than to metazoan fatty acid synthases. Through the dissection of the ApPKS enzyme into mono‐ to didomain fragments and its reconstitution in vitro, we determined its substrate specificity toward different starters and extender units. ApPKS AT domain can effectively transfer acetyl‐CoA and malonyl‐CoA to the ApPKS ACP stand‐alone domain. Furthermore, the KS and KR domains, in the presence of Escherichia coli ACP, acetyl‐CoA, and malonyl‐CoA, showed the ability to catalyze the chain elongation and the β‐keto reduction steps necessary to yield a 3‐hydroxybutyryl‐ACP derivate. These results provide new insights into the catalytic efficiency and specificity of this uncharacterized family of PKSs.
Hsa_circ_101280 promotes hepatocellular carcinoma by regulating miR‐375/JAK2
Authors: Cao Shuang , Wang Guohua , Wang Jia , Li Cheng , Zhang Le 
Published: October 2018

AbstractIn this study, we sought to predict the effects of a certain circular RNA (circRNA), hsa_circ_101280 (also known as hsa_circ_0100929 and hsa_circ_SLAIN1), on hepatocellular carcinoma (HCC) cells and to determine the potential mechanism. After screening differentially expressed circRNAs in HCC tissues through Gene Expression Omnibus data analysis, hsa_circ_101280 was found to be highly expressed, and its high expression was verified in HCC cell lines with qRT‐PCR along with the low expression of its downstream miRNA miR‐375. Colony formation and flow cytometry assays showed that both hsa_circ_101280 silencing and miR‐375 overexpression restrained proliferation and promoted apoptosis in HCC cells. JAK2 was identified as a downstream mRNA target of miR‐375 by RNA pull‐down and dual‐luciferase reporter gene assays, its expression in HCC cell lines were positively regulated by hsa_circ_101280 and negatively by miR‐375 expression. Furthermore, the silencing of hsa_circ_101280 significantly inhibited the growth of HCC xenografts in nude mice, with the downregulated expression of JAK2. Overall, both the in vitro and in vivo studies revealed that hsa_circ_101280 largely facilitated the tumorigenesis of HCC, characterized by the promoted proliferation and suppressed apoptosis of HCC cells, by sponging miR‐375 and upregulating JAK2.
Effects of glufosinate‐ammonium herbicide and pod sealant on spider Pardosa agrestis
Authors: Niedobová Jana , Krištofová Lucie , Michalko Radek , Hula Vladimír , Kýnický Jindřich , Brtnický Martin 
Published: October 2018

AbstractHerbicides based upon glufosinate‐ammonium (GLA) are among the world's most widely used. They also are applied on the most prominent oil crops as desiccants in combination with pod sealants to prevent pod shatter and seed loss close to harvest. Even though these crops occupy a significant part of the world's agroecosystems, the effects of GLA herbicides on non‐target arthropods, and in particular natural enemies of pests, have been studied very rarely, and such effects of pod sealants have never been studied. We studied in our laboratory mortality as well as prey capture efficiency of the common GLA herbicide and desiccant Basta 15®, pod sealant Arrest®, and a mixture of both on the wolf spider Pardosa agrestis. We found that Basta 15® and the mixture had lethal effect on spiders. We also found significant, short‐term effect on predatory activity of spiders after all treatments. Basta 15® significantly influenced the amount of captured prey also in the long term. This is the first study showing lethal effect on spiders of the herbicide and herbicide plus pod sealant mixture. This is also the first study examining the effects of pod sealant on the mortality and predatory activity of a pest antagonist. More studies regarding the effects of agricultural chemical mixes are needed to uncover their effects on beneficial organisms existing within agroecosystems.
"We Take Care of Patients, but We Don't Advocate for Them": Advance Care Planning in Prison or Jail
Authors: Ekaireb Rachel , Ahalt Cyrus , Sudore Rebecca , Metzger Lia , Williams Brie 
Published: October 2018

ObjectivesTo investigate correctional healthcare providers’ knowledge of and experience with advance care planning (ACP), their perspectives on barriers to ACP in correctional settings, and how to overcome those barriers.DesignQualitative.SettingFour prisons in 2 states and 1 large city jail in a third state.ParticipantsCorrectional healthcare providers (e.g., physicians, nurses, social workers; N=24).ResultsParticipants demonstrated low baseline ACP knowledge; 85% reported familiarity with ACP, but only 42% provided accurate definitions. Fundamental misconceptions included the belief that providers provided ACP without soliciting inmate input. Multiple ACP barriers were identified, many of which are unique to prison and jail facilities, including provider uncertainty about the legal validity of ACP documents in prison or jail, inmate mistrust of the correctional healthcare system, inmates’ isolation from family and friends, and institutional policies that restrict use of ACP. Clinicians’ suggestions for overcoming those barriers included ACP training for clinicians, creating psychosocial support opportunities for inmates, revising policies that limit ACP, and systematically integrating ACP into healthcare practice.ConclusionDespite an increasing number of older and seriously ill individuals in prisons and jails, many correctional healthcare providers lack knowledge about ACP. In addition to ACP barriers found in the community, there are unique barriers to ACP in prisons and jails. Future research and policy innovation are needed to develop clinical training programs and identify ACP implementation strategies for use in correctional settings. J Am Geriatr Soc 66:2382–2388, 2018.
How do neonatal units within the Australian and New Zealand Neonatal Network manage ex‐preterm infants with severe chronic lung disease still requiring major respiratory support at term?
Authors: Battin Malcolm R , McKinlay Christopher JD 
Published: October 2018

AimThe aim was to survey the Australian and New Zealand Neonatal Network (ANZNN) member units regarding current services and management guidelines for the ex‐premature infant with severe chronic lung disease (CLD) still requiring significant respiratory support at term.MethodsA 16‐question survey was sent to clinical directors of all Level 3 units in Australia and New Zealand via the network. Reminder emails were sent, as required, to prompt a satisfactory response rate.ResultsSurvey responses were received from 26 of the 29 (90%) ANZNN Level 3 units. At 37 weeks' corrected gestation, over 90% of the units provide ongoing respiratory support in the neonatal intensive care unit (NICU). However, by 50 weeks, ongoing care is provided in several settings, including NICU, high dependency unit (HDU)/paediatric intensive care unit or respiratory wards. The majority (76%) of units arrange transfer on an ad hoc basis, but six units (24%) have set criteria for transfer based on gestation, workload and respiratory requirement. Three units declared a maximum age in NICU (44, 46 or 48 weeks). A variety of approaches were used to identify infants who were likely to require transfer, and 78% of units had a staff member assigned to assist transition. Three units stated that they had a home ventilation programme suitable for these infants. No unit supplied a guideline on tracheostomy or specific respiratory management post‐term.ConclusionDespite a significant number of babies requiring ongoing support for severe CLD, the location of the service appears very variable, and there is a lack of specific written guidelines.