bluuebunny/crossref_metadata_2025_split huggingface dataset:
Management of neutropenic fever in a private hospital oncology unit
Authors: Skiba Rohen , Sikotra Nisha , Ball Timothy , Arellano Astrid , Gabbay Eli , Clay Timothy D. 
Published: August 2019

AbstractBackgroundNeutropenic fever is a medical emergency, which poses a significant morbidity and mortality risk to cancer patients receiving chemotherapy. National guidelines recommend that patients presenting with suspected neutropenic fever receive appropriate intravenous antibiotics within 60 min of admission.AimWe aimed to investigate the management of neutropenic fever in a large private oncology centre.MethodsA retrospective audit of all patients who presented to St John of God Hospital, Subiaco, in the 2017 calendar year, with a known solid organ malignancy and a recorded diagnosis of neutropenic fever was conducted. Patients were identified through the hospitals Patient Administration System and ICD‐10 codes. Information was collected from the hospital medical records using a standardised data collection tool.ResultsThere were 98 admissions relating to 88 patients with neutropenic fever during the study period. The median age was 64 years (range: 23–85 years) with 57 (65%) females. Antibiotic selections consistent with the Australian guidelines were made in 88 (89%) admissions. The mean time to antibiotic administration was 279 min, with a median of 135 min (range: 15–5160 min). Antibiotics were administered within the recommended time frame in only eight (11%) admissions.ConclusionClinicians prescribed antibiotics in accordance with national guidelines; however, there were systemic inefficiencies which resulted in delayed antibiotic initiation. This has resulted in implementation of strategies to minimise delay.
Electrostatic interactions: From immune receptor assembly to signaling
Authors: Connolly Audrey , Gagnon Etienne 
Published: August 2019

AbstractOur ability to mount a long‐lasting and protective immune response relies on a variety of immune receptors that enable the recognition of ongoing infections, which triggers the adaptation of a myriad of immune cells. The organization of several immune receptors, such as the T cells receptor and several natural killer cell receptors, utilizes different modules for ligand recognition and signaling. These receptors require specific recognition mechanisms between the different modules in order to ensure proper assembly and function. Once assembled, immune receptors must remain inactive in the absence of ligand to prevent the onset of unwanted immune response. Indeed, several mechanisms exist to prevent aberrant immune receptor signaling in the absence of ligand to avert the initiation of uncontrolled autoimmunity. However, once a ligand is recognized, immune receptors must rapidly and specifically engage kinases to initiate highly regulated signaling cascades that lead to the initiation of transcriptional programs that dictate the immune response. Over the last decade, compelling evidence have been presented which suggest that electrostatic interactions are critical for many aspects of immune receptor functions. In the work that follows, we present an overview of the literature that have provided evidence that illustrate how electrostatic interactions regulate immune receptor assembly, inactive state, triggering, and signaling.
The TCR is an allosterically regulated macromolecular machinery changing its conformation while working
Authors: Schamel Wolfgang W. , Alarcon Balbino , Minguet Susana 
Published: August 2019

AbstractThe αβ T‐cell receptor (TCR) is a multiprotein complex controlling the activation of T cells. Although the structure of the complete TCR is not known, cumulative evidence supports that the TCR cycles between different conformational states that are promoted either by thermal motion or by force. These structural transitions determine whether the TCR engages intracellular effectors or not, regulating TCR phosphorylation and signaling. As for other membrane receptors, ligand binding selects and stabilizes the TCR in active conformations, and/or switches the TCR to activating states that were not visited before ligand engagement. Here we review the main models of TCR allostery, that is, ligand binding at TCRαβ changes the structure at CD3 and ζ. (a) The ITAM and proline‐rich sequence exposure model, in which the TCR's cytoplasmic tails shield each other and ligand binding exposes them for phosphorylation. (b) The membrane‐ITAM model, in which the CD3ε and ζ tails are sequestered inside the membrane and again ligand binding exposes them. (c) The mechanosensor model in which ligand binding exerts force on the TCR, inducing structural changes that allow signaling. Since these models are complementary rather than competing, we propose a unified model that aims to incorporate all existing data.
mTOR and other effector kinase signals that impact T cell function and activity
Authors: Myers Darienne R. , Wheeler Benjamin , Roose Jeroen P. 
Published: August 2019

AbstractT cells play important roles in autoimmune diseases and cancer. Following the cloning of the T cell receptor (TCR), the race was on to map signaling proteins that contributed to T cell activation downstream of the TCR as well as co‐stimulatory molecules such as CD28. We term this “canonical TCR signaling” here. More recently, it has been appreciated that T cells need to accommodate increased metabolic needs that stem from T cell activation in order to function properly. A central role herein has emerged for mechanistic/mammalian target of rapamycin (mTOR). In this review we briefly cover canonical TCR signaling to set the stage for discussion on mTOR signaling, mRNA translation, and metabolic adaptation in T cells. We also discuss the role of mTOR in follicular helper T cells, regulatory T cells, and other T cell subsets. Our lab recently uncovered that “tonic signals”, which pass through proximal TCR signaling components, are robustly and selectively transduced to mTOR to promote baseline translation of various mRNA targets. We discuss insights on (tonic) mTOR signaling in the context of T cell function in autoimmune diseases such as lupus as well as in cancer immunotherapy through CAR‐T cell or checkpoint blockade approaches.
Disclosure of confidential information by mental health nurses, of patients they assess to be a risk of harm to self or others: An integrative review
Authors: Conlon Darren , Raeburn Toby , Wand Timothy 
Published: August 2019

AbstractThere is a duty of confidentiality on the part of mental health nurses when they handle confidential patient information. Nonetheless, it may be necessary to disclose confidential information of a patient if the patient is assessed as being a risk to self or others, to protect the patient or others from harm. However, disclosing information inappropriately may constitute a breach of confidentiality. There is a paucity of information on how mental health nurses understand the rules of confidentiality when deciding to withhold or disclose confidential information in these circumstances. An integrative review of the literature was undertaken to explore the disclosure of confidential information by mental health nurses when they assess a patient as being a risk of harm. The findings indicate the rules of confidentiality are not well understood, or are not adhered to by mental health nurses. Risk assessments were found to underpin deliberations to withhold or disclose confidential information of a patient, despite risk being difficult to predict with any certainty. For risk assessment, mental health nurses were noted to prefer their unstructured clinical judgement over actuarial methods; and defer to their clinical intuition over scores of a structured risk assessment instrument, when making structured clinical judgement‐backed decisions in this area of their practice. Gaps in the literature that may be addressed by future empirical research were revealed during this integrative review.
Circ_0136474 and MMP‐13 suppressed cell proliferation by competitive binding to miR‐127‐5p in osteoarthritis
Authors: Li Zhao , Yuan Bo , Pei Zheng , Zhang Keshi , Ding Zhentao , Zhu Si , Wang Yichuan , Guan Zhenpeng , Cao Yongping 
Published: August 2019

AbstractOsteoarthritis (OA) is a prevalent degenerative joint disease whose pathogenesis remains unclear. The research aims to investigate the roles of Circ_0136474/miR‐127‐5p/MMP‐13 axis in OA. Differentially expressed circRNAs and miRNAs in OA cartilage tissue were screened out and visualized by R project based on RNA‐seq data and microarray data respectively. qRT‐PCR was carried out for detection of relative expression levels of Circ_0136474, miR‐127‐5p, MMP‐13 and other inflammatory factors and Western blot analysis was conducted to detect the protein expression level of MMP‐13. CCK‐8 assay and flow cytometry were conducted to determine cell proliferation and cell apoptotic ability respectively. RNA‐fluorescence in situ hybridization (RNA‐FISH) experiments were conducted to confirm the immune‐localization of the Circ_0136474 and MMP‐13 in human tissues. Targeted relationships were predicted by bioinformatic analysis and verified by dual‐luciferase reporter assay. Our findings revealed that the expression levels of both Circ_0136474 and MMP‐13 in OA cartilage tissue were significantly higher than that in normal cartilage tissue. Circ_0136474 could suppress cell proliferation by facilitating MMP‐13 expression and suppressing miR‐127‐5p expression in OA. Overexpression of miR‐127‐5p negatively regulated MMP‐13 expression to enhance cell proliferation. Our study demonstrated that Circ_0136474 and MMP‐13 suppressed cell proliferation, while enhanced cell apoptosis by competitive binding to miR‐127‐5p in OA, which may well provide us with a new therapeutic strategy for osteoarthritis.
Up‐regulated CST5 inhibits bone resorption and activation of osteoclasts in rat models of osteoporosis via suppression of the NF‐κB pathway
Authors: Wang Fei , Zhang Chuanzhu , Ge Wei , Zhang Guoqiang 
Published: August 2019

AbstractHere, we aim at exploring the effect of CST5 on bone resorption and activation of osteoclasts in osteoporosis (OP) rats through the NF‐κB pathway. Microarray analysis was used to screen the OP‐related differentially expressed genes. Osteoporosis was induced in rats by intragastric retinoic acid administration. The serum levels of tartrate‐resistant acid phosphatase (TRAP), bone alkaline phosphatase (BALP) and osteocalcin (OC) and the expression of CD61 on the surface of osteoclasts were examined. The number of osteoclasts and the number and area of resorption pits were detected. Besides, the pathological changes and bone mineral density in bone tissues of rats were assessed. Also, the relationship between CST5 and the NF‐κB pathway was identified through determining the expression of CST5, RANKL, RANK, OPG, p65 and IKB. Poorly expressed CST5 was indicated to affect the OP. CST5 elevation and inhibition of the NF‐κB pathway decreased serum levels of TRAP, BALP and OC and expression of CD61 in vivo and in vitro. In OP rats, CST5 overexpression increased trabecular bones and bone mineral density of bone tissues, but decreased trabecular separation, fat within the bone marrow cavities and the number of osteoclasts through inhibiting the NF‐κB pathway. In vivo experiments showed that CST5 elevation inhibited growth in number and area of osteoclastic resorption pits and restrained osteoclastic bone absorption by inhibiting the NF‐κB pathway. In summary, overexpression of CST5 suppresses the activation and bone resorption of osteoclasts by inhibiting the activation of the NF‐κB pathway.
Anatomically specific reactive oxygen species production participates in Marfan syndrome aneurysm formation
Authors: Emrich Fabian , Penov Kiril , Arakawa Mamoru , Dhablania Nathan , Burdon Grayson , Pedroza Albert J. , Koyano Tiffany K. , Kim Young M. , Raaz Uwe , Connolly Andrew J. , Iosef Cristiana , Fischbein Michael P. 
Published: August 2019

AbstractMarfan syndrome (MFS) is a connective tissue disorder that results in aortic root aneurysm formation. Reactive oxygen species (ROS) seem to play a role in aortic wall remodelling in MFS, although the mechanism remains unknown. MFS Fbn1C1039G/+ mouse root/ascending (AS) and descending (DES) aortic samples were examined using DHE staining, lucigenin‐enhanced chemiluminescence (LGCL), Verhoeff's elastin‐Van Gieson staining (elastin breakdown) and in situ zymography for protease activity. Fbn1C1039G/+ AS‐ or DES‐derived smooth muscle cells (SMC) were treated with anti‐TGF‐β antibody, angiotensin II (AngII), anti‐TGF‐β antibody + AngII, or isotype control. ROS were detected during early aneurysm formation in the Fbn1C1039G/+ AS aorta, but absent in normal‐sized DES aorta. Fbn1C1039G/+ mice treated with the unspecific NADPH oxidase inhibitor, apocynin reduced AS aneurysm formation, with attenuated elastin fragmentation. In situ zymography revealed apocynin treatment decreased protease activity. In vitro SMC studies showed Fbn1C1039G/+‐derived AS SMC had increased NADPH activity compared to DES‐derived SMC. AS SMC NADPH activity increased with AngII treatment and appeared TGF‐β dependent. In conclusion, ROS play a role in MFS aneurysm development and correspond anatomically with aneurysmal aortic segments. ROS inhibition via apocynin treatment attenuates MFS aneurysm progression. AngII enhances ROS production in MFS AS SMCs and is likely TGF‐β dependent.
Comorbid Depressive Symptoms and Chronic Medical Conditions Among US Chinese Older Adults
Authors: Kong Dexia , Solomon Phyllis , Dong XinQi 
Published: August 2019

OBJECTIVESThe prevalence and health consequences of comorbid depressive symptoms (DSs) and chronic medical conditions (CMCs) among older ethnic minority populations remain poorly understood. To bridge this gap, the present cross‐sectional study examined the prevalence of comorbid DS‐CMC and the association between such comorbidity and health services use among US Chinese older adults.DESIGN AND SETTINGData were from the Population Study of Chinese Elderly in Chicago (N = 3157). The relationship between comorbid DS‐CMC and health service use (ie, emergency department [ED] visits and hospitalizations) was investigated by stratifying the sample into four groups: (1) neither DSs nor CMCs (ie, heart disease, stroke, cancer, high cholesterol, diabetes, high blood pressure, hip fraction, thyroid, and osteoarthritis); (2) DSs only; (3) CMCs only; and (4) comorbid DS‐CMC. Multivariate negative binomial regression models were conducted to determine the relationship between comorbid DS‐CMC and health service use.RESULTSParticipants were 73 years old on average. The prevalence of comorbid DSs ranged between 0.7% and 4.6% across various CMCs. The odds of DSs were at least twice as high among US Chinese older adults with CMCs than those without the various conditions. Compared with US Chinese older adults with neither DSs nor CMCs, those with comorbid DS‐CMC had more ED visits (rate ratio [RR] = 3.32; 95% confidence interval [CI] = 2.03‐5.42) and hospitalizations (RR = 3.12; 95% CI = 1.95‐4.97).CONCLUSIONRecognition and treatment of comorbid DS‐CMC warrant increased policy and clinical attention. The findings underscore the potential need to develop effective services targeting DSs among US Chinese older adults with CMCs. J Am Geriatr Soc 67:S545–S550, 2019.
Sources and Variations in Social Support and Risk for Elder Mistreatment in a US Chinese Population
Authors: Zheng Shenglin , Li Mengting , Kong Dexia , Dong XinQi 
Published: August 2019

OBJECTIVESResearch has examined the relationships between positive social support (PSS) and elder mistreatment (EM) but less is known regarding the negative aspect of social support (NSS), especially among minority groups in the United States. This study aimed to investigate the relationships between PSS/NSS from different sources and EM among US Chinese older adults.DesignPopulation‐based cross‐sectional study.SettingGreater Chicago, IL, area.PARTICIPANTSA representative sample of Chinese older adults aged 60 years or older (N = 3157) from the Population Study of ChINese Elderly in Chicago in 2011 to 2013.MeasurementsWe applied a 10‐item widely used instrument to assess EM. PSS and NSS from spouse/family members/friends were measured by a 12‐item scale. Multivariate logistic regression analyses were conducted to examine the relationships.RESULTSAfter adjusting for confounders, higher levels of overall PSS from all three sources, including spouse, family members, and friends (odds ratio [OR] = 0.88 [95% confidence interval {CI} = 0.85‐0.91]), were associated with lower risk of EM. But participants with a higher level of overall NSS from all three sources (OR = 1.51 [95% CI = 1.41‐1.61]) were more likely to experience EM. The results on the relationships between PSS from spouse (OR = 0.70 [95% CI = 0.64‐0.76]), PSS from family members (OR = 0.73 [95% CI = 0.68‐0.79]), and EM were similar to overall PSS. But PSS from friends had a nonsignificant association with EM. Greater levels of NSS from spouse (OR = 1.84 [95% CI = 1.64‐2.07]), family members (OR = 2.36 [95% CI = 2.03‐2.75]), and friends (OR = 1.69 [95% CI = 1.32‐2.17]) were associated with increased risks of EM.CONCLUSIONHigher levels of SS were not always associated with lower risks of EM among US Chinese older adults. NSS might have counter effects. Future qualitative or longitudinal research needs to explore detailed cultural explanations and casual relationships between SS and EM. J Am Geriatr Soc 67:S499–S505, 2019.
Implantable Cardioverter‐Defibrillators and Cardiac Resynchronization Therapy in Older Adults With Heart Failure
Authors: Sandhu Amneet , Levy Andrew , Varosy Paul D. , Matlock Daniel 
Published: August 2019

BACKGROUND/OBJECTIVESImplantable cardioverter‐defibrillators (ICDs) and cardiac resynchronization therapy (CRT) are cardiac implantable electronic devices that may improve morbidity and mortality in select patients with heart failure. Although the benefits of these devices have been well defined, competing mortality risks, comorbid conditions, and frailty pose difficulty in determining risk‐benefit trade‐offs when these options are considered for older adults.CONCLUSIONIn this review, we focus on the benefit, risk, and use of ICD and CRT in older adults, particularly because the goals of care for many older adults include a shift away from life‐prolonging interventions. Additionally, we discuss periprocedural risk, cost, and maintenance in older populations. Finally, we introduce a framework for helping clinicians and older adults make these challenging decisions collectively. J Am Geriatr Soc 67:2193–2199, 2019
30‐Day Emergency Department Revisit Rates among Older Adults with Documented Dementia
Authors: Kent Tyler , Lesser Adriane , Israni Juhi , Hwang Ula , Carpenter Christopher , Ko Kelly J. 
Published: August 2019

OBJECTIVESPublished literature on national emergency department (ED) revisit rates among older adults with dementia is sparse, despite anecdotal evidence of higher ED utilization. Thus we evaluated the odds ratio (OR) of 30‐day ED revisits among older adults with dementia using a nationally representative sample.DESIGNWe assessed the frequency of claims associated with a 30‐day ED revisit among Medicare beneficiaries with and without a dementia diagnosis before or at index ED visit. We used a logistic regression model controlling for dementia, age, sex, race, region, Medicaid status, transfer to a skilled nursing facility after ED, primary care physician use 12 months before index, and comorbidity.SETTINGA nationally representative sample of claims data for Medicare beneficiaries aged 65 and older who maintained continuous fee‐for‐service enrollment during 2015 and 2016. Only outpatient claims associated with an ED visit between January 2016 and November 2016 were included as a qualifying index encounter.PARTICIPANTSWe identified 240 249 patients without dementia and 54 622 patients for whom a dementia code was recorded in the year before the index encounter in 2016.RESULTSOur results indicate a significant difference in unadjusted 30‐day ED revisit rates among those with an ED dementia diagnoses (22.0%) compared with those without (13.9%). Our adjusted results indicated that dementia is a significant predictor of 30‐day ED revisits (P < .0001). Those with a dementia diagnosis at or before the index ED visit were more likely to have experienced an ED revisit within 30 days (OR = 1.27; 95% confidence interval = 1.24‐1.31).CONCLUSIONDementia diagnoses were a significant predictor of 30‐day ED revisits. Further research should assess potential reasons why dementia is associated with markedly higher revisit rates, as well as opportunities to manage and transition dementia patients from the ED back to the community more effectively. J Am Geriatr Soc 67:2254–2259, 2019
Characteristics of the transverse 2D uniserial arrangement of rows of decussating enamel rods in the inner enamel layer of mouse mandibular incisors
Authors: Smith Charles E. , Hu Yuanyuan , Hu Jan C‐C. , Simmer James P. 
Published: August 2019

AbstractThe 2D arrangement of rows of enamel rods with alternating (decussating) tilt angles across the thickness of the inner layer in rat and mouse incisor enamel is well known and assumed to occur in a uniform and repetitive pattern. Some irregularities in the arrangement of rows have been reported, but no detailed investigation of row structure across the entire inner enamel layer currently exists. This investigation was undertaken to determine if the global row pattern in mouse mandibular incisor enamel is predominately regular in nature with only occasional anomalies or if rows of enamel rods have more spatial complexity than previously suspected. The data from this investigation indicate that rows of enamel rods are highly variable in length and have complex transverse arrangements across the width and thickness of the inner enamel layer. The majority of rows are short or medium in length, with 87% having < 100 rods per row. The remaining 13% are long rows (with 100–233 rods per row) that contain 46% of all enamel rods seen in transverse sections. Variable numbers of rows were associated with the lateral, central and mesial regions of the enamel layer. Each region contained different ratios of short, medium and long rows. A variety of relationships was found along the transverse length of rows in each region, including uniform associations of alternating rod tilts between neighboring rows, and instances where two rows having the same rod tilt were paired for variable distances then moved apart to accommodate rows of opposite tilt. Sometimes a row appeared to branch into two rows with the same tilt, or conversely where two rows merged into one row depending upon the mesial‐to‐lateral direction in which the row was viewed. Some rows showed both pairing and branching/merging along their length. These tended to be among the longest rows identified, and they often crossed the central region with extensions into the lateral and mesial regions. The most frequent row arrangement was a row of petite length nestled at the side of another row having the same rod tilt (30% of all rows). These were termed ‘focal stacks’ and may relate to the evolution of uniserial rat and mouse incisor enamel from a multilayered ancestor. The mesial and lateral endpoints of rows also showed complex arrangements with the dentinoenamel junction (DEJ), the inner enamel layer itself, and the boundary area to the outer enamel layer. It was concluded that the diversity in row lengths and various spatial arrangements both within and between rows across the transverse plane provides a method to interlock the enamel layer across each region and keep the enamel layer compact relative to the curving DEJ surface. The uniserial pattern for rows in mouse mandibular incisors is not uniform, but diverse and very complex.