bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identifying critically important vascular access outcomes for trials in haemodialysis: an international survey with patients, caregivers and health professionals
Authors: Viecelli Andrea K , Howell Martin , Tong Allison , Teixeira-Pinto Armando , O’Lone Emma , Ju Angela , Craig Jonathan C , Hooi Lai-Seong , Lee Timmy , Lok Charmaine E , Polkinghorne Kevan R , Quinn Robert R , Vachharajani Tushar J , Vanholder Raymond , Zuo Li , Tordoir Jan , Pecoits-Filho Roberto , Yuo Theodore , Kopperschmidt Pascal , Smith Rob , Irish Ashley B , Mori Trevor A , Pascoe Elaine M , Johnson David W , Hawley Carmel M 
Published: July 2019

Abstract

Background
Vascular access outcomes reported across haemodialysis (HD) trials are numerous, heterogeneous and not always relevant to patients and clinicians. This study aimed to identify critically important vascular access outcomes.

Method
Outcomes derived from a systematic review, multi-disciplinary expert panel and patient input were included in a multilanguage online survey. Participants rated the absolute importance of outcomes using a 9-point Likert scale (7–9 being critically important). The relative importance was determined by a best–worst scale using multinomial logistic regression. Open text responses were analysed thematically.

Results
The survey was completed by 873 participants [224 (26%) patients/caregivers and 649 (74%) health professionals] from 58 countries. Vascular access function was considered the most important outcome (mean score 7.8 for patients and caregivers/8.5 for health professionals, with 85%/95% rating it critically important, and top ranked on best–worst scale), followed by infection (mean 7.4/8.2, 79%/92% rating it critically important, second rank on best–worst scale). Health professionals rated all outcomes of equal or higher importance than patients/caregivers, except for aneurysms. We identified six themes: necessity for HD, applicability across vascular access types, frequency and severity of debilitation, minimizing the risk of hospitalization and death, optimizing technical competence and adherence to best practice and direct impact on appearance and lifestyle.

Conclusions
Vascular access function was the most critically important outcome among patients/caregivers and health professionals. Consistent reporting of this outcome across trials in HD will strengthen their value in supporting vascular access practice and shared decision making in patients requiring HD.
Immunostaining for galactose-deficient immunoglobulin A is not specific for primary immunoglobulin A nephropathy
Authors: Cassol Clarissa A , Bott Cherri , Nadasdy Gyongyi M , Alberton Valeria , Malvar Ana , Nagaraja Haikady N , Nadasdy Tibor , Rovin Brad H , Satoskar Anjali A 
Published: July 2019

Abstract

Background
Primary immunoglobulin A nephropathy (IgAN) is characterized by IgA1-dominant or codominant glomerular deposits, postulated to be galactose deficient (Gd). However, glomerular IgA deposition can also occur in nonrenal diseases such as liver cirrhosis, psoriasis and inflammatory bowel disease (‘secondary IgAN’) or be an incidental finding in biopsies with other pathologies. A glomerulonephritis resembling IgAN can develop in patients with bacterial, mainly staphylococcal infections [staphylococcal infection-associated glomerulonephritis (SAGN)]. There are no specific histological features to distinguish between these, but differentiation is critical for appropriate management. The aim of this study was to investigate whether a recently described antibody to Gd-IgA1 (KM-55) could aid in differentiating primary IgAN from other conditions with glomerular IgA deposition, especially SAGN.

Methods
We performed a retrospective cohort study of patients who underwent kidney biopsy for clinical indications and were found to have glomerular IgA deposits.

Results
We evaluated 100 biopsies, including primary IgAN (n = 44), secondary IgAN (n = 27), SAGN (n = 13), incidental IgA deposition (n = 8) and lupus nephritis (n = 8). There was no difference in Gd-IgA staining intensity or the proportion of positive cases between primary and secondary IgAN. SAGN and cases with incidental IgA deposits had significantly lower Gd-IgA staining intensity than primary IgAN, but up to 69% of SAGN cases were positive (albeit weaker).

Conclusions
Gd-IgA staining is present not only in primary IgAN, but also in biopsies with secondary IgAN, SAGN and incidental IgA. Weak or negative staining may favor SAGN, especially in the setting of infection, or incidental IgA in the absence of nephritic symptoms or in the presence of other unrelated glomerular pathologies. However, positive staining for Gd-IgA alone is not specific enough for a diagnosis of primary IgAN.
Targeting hypoxia downstream signaling protein, CAIX, for CAR T-cell therapy against glioblastoma
Authors: Cui Jing , Zhang Qi , Song Qi , Wang Herui , Dmitriev Pauline , Sun Mitchell Y , Cao Xiaoyu , Wang Yang , Guo Liemei , Indig Iris H , Rosenblum Jared S , Ji Chunxia , Cao Dongqing , Yang Kaiyong , Gilbert Mark R , Yao Yu , Zhuang Zhengping 
Published: July 2019

Abstract

Background
Glioblastoma survival remains unchanged despite continuing therapeutic innovation. Herein, we aim to (i) develop chimeric antigen receptor (CAR) T cells with a specificity to a unique antigen, carbonic anhydrase IX (CAIX), which is expressed in the hypoxic microenvironment characteristic of glioblastoma, and (ii) demonstrate its efficacy with limited off-target effects.

Methods
First we demonstrated expression of CAIX in patient-derived glioblastoma samples and available databases. CAR T cells were generated against CAIX and efficacy was assessed in 4 glioblastoma cell lines and 2 glioblastoma stem cell lines. Cytotoxicity of anti-CAIX CAR T cells was assessed via interferon gamma, tumor necrosis factor alpha, and interleukin-2 levels when co-cultured with tumor cells. Finally, we assessed efficacy of direct intratumoral injection of the anti-CAIX CAR T cells on an in vivo xenograft mouse model using the U251 luciferase cell line. Tumor infiltrating lymphocyte analyses were performed.

Results
We confirm that CAIX is highly expressed in glioblastoma from patients. We demonstrate that CAIX is a suitable target for CAR T-cell therapy using anti-CAIX CAR T cells against glioblastoma in vitro and in vivo. In our mouse model, a 20% cure rate was observed without detectable systemic effects.

Conclusions
By establishing the specificity of CAIX under hypoxic conditions in glioblastoma and highlighting its efficacy as a target for CAR T-cell therapy, our data suggest that anti-CAIX CAR T may be a promising strategy to treat glioblastoma. Direct intratumoral injection increases anti-CAIX CAR T-cell potency while limiting its off-target effects.
Acyl chain that matters: introducing sn-2 acyl chain preference to a phospholipase D by protein engineering
Authors: Damnjanović Jasmina , Nakano Hideo , Iwasaki Yugo 
Published: July 2019

AbstractPhospholipase D (PLD) is an enzyme widely used for enzymatic synthesis of structured phospholipids (PLs) with modified head groups. These PLs are mainly used as food supplements and liposome ingredients. Still, there is a need for an enzyme that discriminates between PLs and lysoPLs, for specific detection of lysoPLs in various specimens and enzymatic synthesis of certain PLs from a mixed substrate. To meet this demand, we aimed at altering sn-2 acyl chain recognition of a PLD, leading to a variant enzyme preferably reacting on lysoPLs, by protein engineering. Based on the crystal structure of Streptomyces antibioticus PLD, W166 was targeted for saturation mutagenesis due to its strong interaction with the sn-2 acyl chain of the PL. Screening result pointed at W166R and W166K PLDs to selectively react on lysophosphatidylcholine (lysoPC), while not on PC. These variants showed a negative correlation between activity and sn-2 chain length of PL substrates. This behavior was not observed in the wild-type (WT)-PLD. Kinetic analysis revealed that the W166R and W166K variants have 7–10 times higher preference to lysoPC compared to the WT-PLD. Additionally, W166R PLD showed detectable activity toward glycero-3-phosphocholine, unlike the WT-PLD. Applicability of the lysoPC-preferring PLD was demonstrated by detection of lysoPC in the mixed PC/lysoPC sample and by the synthesis of cyclic phosphatidic acid. Structure model analyses supported the experimental findings and provided a basis for the structure model-based hypothesis on the observed behavior of the enzymes.
Inequality in access to hearing care for older adults in residential homes
Authors: White J D , Johnson C , Deplacido C G , Matthews B , Steenkamp E H 
Published: July 2019

Abstract

Background
The population of older people in residential homes is projected to rise. There are unrecognized hearing difficulties among residents and prevalence of hearing loss in this population is underreported. This can result in an overestimation of levels of cognitive impairment. Untreated hearing loss is associated with social isolation, depression, disruptive behaviour and cognitive decline. This study aimed to explore the provision of hearing care (hearing assessment, rehabilitation and staff training) in Scottish care homes for older people.

Methods
A survey comprising 18 questions was distributed to the managers (or designated staff members) of 659 care homes across Scotland.

Results
Responses were obtained from 154 care homes. The results support existing evidence that hearing is not assessed in the majority of homes, resulting in under detection of hearing loss. Staff lack training in supporting residents’ hearing needs. Access to hearing care in residential homes differs across health board areas.

Conclusions
There is an urgent requirement for hearing assessment of older adults on admission to residential care. Care providers require this information to construct effective care plans and mitigate the effects of hearing loss. Those responsible for providing hearing rehabilitation services require information about service users to address any unmet need.
Analysing the determinants of higher education systems’ performance–a structural equation modelling approach
Authors: Agasisti Tommaso , Bertoletti Alice 
Published: July 2019

Abstract
This article deals with the relationships between the performance of higher education systems (HESs) and their potential determinants. The research employed data relating to twenty-nine European countries, within a time span of 15 years. The empirical work is based on a conceptual framework that has been tested through Structural Equation Modelling. The data was selected from a novel data set that we have built by gathering HES indicators from the major international databases. Among the more noteworthy results, we found no statistically significant correlation between graduation rates and research performance. Additionally, we found a moderate effect of public expenditure on HES performance. The article addresses the issue of the lack of a comprehensive set of systemic indicators for HES performance, providing a holistic picture of the relationship between HES determinants and performance, which, in turn, could help to provide an adequate evaluation of the policies in the field of higher education.
Governing research through affects: The case of ecosystem services science
Authors: Brunet Lucas , Arpin Isabelle , Peltola Taru 
Published: July 2019

AbstractDespite the abundant literature on transformation of research and the affective dimension of research practice, affective governing of research has not been documented to the same extent. To address this gap, we examine how scientific research can be affectively governed by research institutions. We focus on the case of ecosystem services science, an interdisciplinary field of research expected to lead to decisions capable of halting environmental degradation. Drawing on theoretical discussions bridging the concept of affect and the Foucauldian concept of government, we argue that affects can be mobilised as a technology of government in governing scientific practice. We identify three affective techniques used to govern ecosystem service research and discuss the limits of governing research through affects. Our analysis deepens the understanding of how academic work is transformed in the context of redefined relations between science and society.
R&D and innovation policy in the Western Balkans: Are there additionality effects?
Authors: Orlic Edvard , Radicic Dragana , Balavac Merima 
Published: July 2019

Abstract
This article examines three types of additionality—input, output, and behavioural—in a cross-country framework. Besides conducting a systemic evaluation, which is scarce even in developed economies, this is among the first studies to investigate the effectiveness of R&D and innovation policy in transition economies. We estimate treatment effects for small and medium-sized firms in six Western Balkan countries. Empirical findings from matching estimators indicate no input and output additionality, while we find evidence of behavioural additionality. These results highlight the importance of conducting a systemic evaluation of innovation public support. We discuss theoretical and policy implications stemming from our empirical findings.
Cadmium Exposure Impairs Adult Hippocampal Neurogenesis
Authors: Wang Hao , Abel Glen M , Storm Daniel R , Xia Zhengui 
Published: July 2019

Abstract
Cadmium (Cd) is an environmental pollutant of considerable interest throughout the world and potentially a neurotoxicant. Our recent data indicate that Cd exposure induces impairment of hippocampus-dependent learning and memory in mice. However, the underlying mechanisms for this defect are not known. The goal of this study was to determine if Cd inhibits adult neurogenesis and to identify underlying signaling pathways responsible for this impairment. Adult hippocampal neurogenesis is a process in which adult neural progenitor/stem cells (aNPCs) in the subgranular zone (SGZ) of the dentate gyrus (DG) generate functional new neurons in the hippocampus which contributes to hippocampus-dependent learning and memory. However, studies concerning the effects of neurotoxicants on adult hippocampal neurogenesis and the underlying signaling mechanisms are limited. Here, we report that Cd significantly induces apoptosis, inhibits proliferation, and impairs neuronal differentiation in primary cultured aNPCs derived from the SGZ. In addition, the c-Jun NH2-terminal kinase and p38 mitogen-activated protein kinase signaling pathways are activated by Cd and contribute to its toxicity. Furthermore, we exposed 8-week-old male C57BL/6 mice to Cd through drinking water for 13 weeks to assess the effects of Cd on adult hippocampal neurogenesis in vivo. Cd treatment reduced the number of 5-week-old adult-born cells in the DG and impaired the differentiation of adult-born hippocampal neurons. These results suggest that Cd exposure impairs adult hippocampal neurogenesis both in vitro and in vivo. This may contribute to Cd-mediated inhibition of hippocampus-dependent learning and memory.
Polycystic ovary syndrome
Authors: Pfieffer Mary Lauren 
Published: July 2019

Abstract:
Polycystic ovary syndrome (PCOS) is a common endocrine disorder. Patients may present with a combination of hyperandrogenism symptoms, menstrual irregularities, metabolic syndrome, infertility, acne, and obesity. PCOS diagnosis is based on three diagnostic guidelines. Treatment options include oral contraceptive pills, antiandrogens, and metformin.
Validity of the Budapest Criteria For Poststroke Complex Regional Pain Syndrome
Authors: Oh Sang-Wook , Choi Seong-Uk , Park Mina , Shin Joon-Ho 
Published: July 2019

Objectives:
Complex regional pain syndrome-1 is a chronic neuropathic disorder, and poststroke complex regional pain syndrome (PS-CRPS) is not a rare complication. There is a lack of study implementing the Budapest criteria for PS-CRPS diagnosis. Thus, the present study investigated the validity of the Budapest criteria for PS-CRPS diagnosis and assessed the PS-CRPS–related factors in stroke patients with an affected upper extremity.

Methods:
The study included 72 patients with first-ever stroke resulting in hemiplegia. The prevalence of PS-CRPS and diagnostic validity were compared among the Budapest clinical criteria, Budapest research criteria, modified Budapest criteria (removal of the motor factor from the motor/trophic category), and International Association for the Study of Pain (IASP) criteria in patients diagnosed with PS-CRPS according to the Budapest clinical criteria.

Results:
PS-CRPS was diagnosed in 6 (8.3%), 1 (1.4%), 6 (8.3%), and 11 patients (15.3%) according to the Budapest clinical criteria, Budapest research criteria, modified Budapest criteria, and IASP criteria, respectively. The Budapest criteria and IASP criteria had sensitivities of 0.99 and 1.00, respectively, and specificities of 0.68 and 0.41, respectively, for PS-CRPS diagnosis. There were no differences in risk factors between PS-CRPS patients and non–PS-CRPS patients when the diagnosis was based on the Budapest clinical criteria. However, there were differences in muscle strength and Brunnstrom stage between PS-CRPS patients and non–PS-CRPS patients when the diagnosis was based on the IASP criteria.

Discussion:
Our findings indicate that the diagnostic validity of the current Budapest clinical criteria for PS-CRPS is low. Thus, the current Budapest criteria might not be appropriate for PS-CRPS diagnosis.
Use of Potassium Hydroxide (KOH) Test Reduces Antifungal Medication Prescription for Suspected Monilial Diaper Dermatitis in the Neonatal Intensive Care Unit
Authors: Campbell Julie , MacConnell Valerie , Sacco Lauren , Zuill Ramona , Bosque Elena 
Published: July 2019

Background:Despite availability of rapid fungal potassium hydroxide (KOH) tests, many care providers rely on visual assessment to determine the diagnosis of monilial diaper dermatitis (MDD).Purpose:To determine whether a KOH test, when MDD is suspected, would result in more accurate diagnoses, with decreased antifungal medication prescription and exposure.Methods:Quality improvement project from 2016 through 2017 with protocol implemented in 2017 for treatment of MDD after positive KOH testing. If monilial rash suspected, after 2 negative KOH tests, then antifungal ordered (considered false negative). χ2testing and cost determination were performed.Sample:Neonates in 2 level III neonatal intensive care units.Outcome Variables:KOH test results, use of antifungal medication, and cost.Results:The patient census included 1051 and 1015 patients in the year before and after the protocol initiation. The medical orders for antifungal medication decreased from 143 to 36 (P< .001; 95% odds ratio confidence interval, 2.24-4.38). There was a 75% reduction in both use and cost, as charged, of antifungal agents. Overall charges, including KOH test costs, decreased by 12%. Three infants received multiple negative KOH tests, then a positive one. These met the definition of false-negative tests, per protocol. There were no cases of fungal sepsis.Implications for Practice:Use of a quality improvement protocol, in which the use of KOH testing is required, before antifungal agents are prescribed, results in decreased exposure and costs.Implications for Research:To test the feasibility of bedside “point-of-care” KOH testing, and whether KOH testing and reduced antifungal medication use affects antimicrobial resistance or invasive fungal sepsis.
Zika autoimmunity and Guillain–Barré syndrome
Authors: Katz Itai , Gilburd Boris , Shovman Ora 
Published: July 2019

Purpose of review
To summarize the recent data regarding Guillain–Barré syndrome (GBS) as an autoimmune disorder following infection with Zika virus (ZIKV) infection, including the proposed pathogenic mechanisms and the role of autoantibodies.

Recent findings
The loss of self-tolerance that leads to autoimmune diseases is a multifactorial process that may be illustrated as ‘the mosaic of autoimmunity’. Infectious agents may contribute to the development of autoimmunity by several proposed mechanisms. One of the central mechanisms is molecular mimicry, which is also the most plausible mechanism in the case of ZIKV-induced autoimmune disorders.
A recent meta-analysis found a low prevalence of GBS associated with ZIKV infection. Nevertheless, the estimated cost of illness for patients with GBS associated with ZIKV are tremendous and exceed 4.7 million dollars per year in Brazil alone.

Summary
Currently, there is sufficient data to indicate that ZIKV infection is one of many triggers and factors that may contribute to the development GBS. Thus, it is advised to evaluate and determine ZIKV exposure and infection in the management of potential GBS patients.
Cutaneous Nodular Amyloidosis: A Disfiguring Aspect of the Face
Authors: Dupont Letícia , Martins Souza Paulo Ricardo , Damiani Leandro , Boff Ana Letícia 
Published: July 2019

Abstract:
Primary localized cutaneous nodular amyloidosis is a rare plasma cell dyscrasia in which an amorphous material consisting of light chain amyloid is produced and deposited in the dermis, with varied clinical presentation. We describe the case with unusual and tumor lush clinical presentation in the face with no progression to systemic disease and no evidence of extracutaneous commitment.
Melanotic Schwannoma of the Vulva: A Case Report and Review of the Literature
Authors: Cohen Jarish N. , Yeh Iwei , LeBoit Philip E. 
Published: July 2019

Abstract:
Melanotic schwannoma is a pigmented tumor of peripheral nerve differentiation. Primary cutaneous presentations are extremely rare, as the bulk of melanotic schwannomas tend to develop in paraspinal and axial sites. Tumors arise sporadically and in the setting of the Carney complex. Alterations in the gene encoding protein kinase A regulatory subunit-α (PRKAR1A) underlie most patients with the Carney complex and mediate melanotic schwannoma tumorigenesis. Melanotic schwannomas from noncutaneous sites can locally recur and metastasize widely, leading to a recent proposal to change the nomenclature to “malignant melanotic schwannian tumor.” However, the clinicopathologic features of primary cutaneous melanotic schwannomas are relatively unexplored. We present a case of a nodule arising on the vulva of a 34-year-old woman. Microscopically, a dermal-based, heavily pigmented proliferation of plump spindled and epithelioid cells arrayed in nodules and fascicles was seen. Lesional cells stained positively for S100, Melan-A, and BAP1 but were negative for Prkar1α. Next-generation sequencing of a panel of 480 cancer-associated genes revealed that the tumor harbored a PRKAR1A p.S299fs truncating mutation and copy neutral loss of heterozygosity of chromosome 17q, the locus at which PRKAR1A resides. Importantly, no other genetic abnormalities or chromosomal copy number changes were identified. On the basis of combined histopathologic, immunohistochemical, and genetic features, a diagnosis of melanotic schwannoma was rendered. Overall, we present the first clinicopathologic description of a vulvar melanotic schwannoma, review the literature concerning cutaneous presentations of melanotic schwannoma, and propose that melanotic schwannian tumors native to skin may behave more indolently than their noncutaneous counterparts.