bluuebunny/crossref_metadata_2025_split huggingface dataset:
Informal Caregivers’ Perceptions of Needs From Hospice Providers: An Integrative Review
Authors: Engbers Ruth Anne 
Published: April 2019

Introduction: In the United States, informal caregivers (ICs) provide care to over 70% of patients at the end of life. Approximately 500 000 ICs contribute to the end-of-life care for patients in the United Kingdom. Hospice care is expanding worldwide to meet the needs of these ICs. Because ICs play an instrumental role in the provision of hospice services, and their perspective of their needs of formal services requires further clarity, the purpose of this review is to synthesize research that elucidates perceptions of ICs regarding their experiences with hospice providers. Methods: Twelve research studies regarding perceptions of informal hospice caregivers were obtained by searching CINAHL, PsycINFO, and MEDLINE databases. Results: Four primary themes emerged that describe what ICs perceive as beneficial contributions of hospice providers in aiding their caregiving: providing easy access to desired care, building up the caregiver, forming a relationship, and utilizing culturally relevant interpersonal skills. Conclusion: Particular attention must be paid to ensuring that the IC is acknowledged as an expert part of the team. Clearly explaining available services, creating better ways to ease the IC’s transition from caregiving to bereavement, and recruiting minority hospice providers are other important efforts that could improve the caregiving experience. The needs of ICs are complex, but by listening to their perspective, we can begin to clarify the best ways to aid them in their difficult job.
Long-term survivors of cardiac arrest: A narrative inquiry
Authors: Haydon Gunilla , van der Riet Pamela , Inder Kerry 
Published: April 2019

Background: Despite extensive knowledge and research in cardiac health there is limited understanding in how a cardiac arrest influences the life of long-term survivors. Objective: The aim of this study was to explore how long-term survivors of a cardiac arrest adjusted to their new reality, expressed in their re-storied narratives. Methods: Seven individuals surviving a cardiac arrest 5–26 years ago were interviewed through in-depth conversations over a six-month period. These interviews were analysed using Clandinin and Connelly’s framework of narrative inquiry. Results: Seven threads were found: Disbelief, Surveillance of their body, Loss of control and desire for normality, Keeping fit and informing others, Gratefulness, Spirituality – luck and fate, and Fragility of life and dying. Conclusions: All seven long-term survivors of cardiac arrest expressed a positive attitude. Despite the nature of the cardiac arrest and the hurdles that followed, they have a heightened appreciation for life. This indicates that after the adaptation to their new reality of being a cardiac arrest survivor life returns to a new normality.
Engineered Bcor mutations lead to acute leukemia of progenitor B-1 lymphocyte origin in a sensitized background
Authors: Yin Mianmian , Chung Yang Jo , Lindsley R. Coleman , Walker Robert L. , Zhu Yuelin J. , Ebert Benjamin L. , Meltzer Paul S. , Aplan Peter D. 
Published: April 2019

Abstract
Approximately 10% of NUP98-PHF23 (NP23) mice develop an aggressive acute lymphoblastic leukemia of B-1 lymphocyte progenitor origin (pro-B1 ALL), accompanied by somatic frameshift mutations of the BCL6 interacting corepressor (Bcor) gene, most commonly within a 9-bp “hotspot” in Bcor exon 8. To determine whether experimentally engineered Bcor mutations would lead to pro-B1 ALL, we used clustered, regularly interspaced, short palindromic repeats–associated protein 9 to introduce a Bcor frameshift mutation into NP23 hematopoietic stem and progenitor cells through the use of Bcor small guide RNAs (Bcor sgRNAs). Recipient mice transplanted with NP23 bone marrow or fetal liver cells that had been transduced with a Bcor sgRNA developed pro-B1 ALL, characterized by a B-1 progenitor immunophenotype, clonal Igh gene rearrangement, and Bcor indel mutation, whereas control recipients did not. Similar to a subset of human B-cell precursor ALL, the murine pro-B1 ALL had acquired somatic mutations in Jak kinase genes. JAK inhibitors (ruxolitinib and tofacitinib) inhibited the growth of pro-B1 ALL cell lines established from Bcor sgRNA/NP23 recipients at clinically achievable concentrations (100 nM). Our results demonstrate that Bcor mutations collaborate with NP23 to induce pro-B1 ALL, and that JAK inhibitors are potential therapies for pro-B1 ALL.
Recommendations for the management of hemophagocytic lymphohistiocytosis in adults
Authors: La Rosée Paul , Horne AnnaCarin , Hines Melissa , von Bahr Greenwood Tatiana , Machowicz Rafal , Berliner Nancy , Birndt Sebastian , Gil-Herrera Juana , Girschikofsky Michael , Jordan Michael B. , Kumar Ashish , van Laar Jan A. M. , Lachmann Gunnar , Nichols Kim E. , Ramanan Athimalaipet V. , Wang Yini , Wang Zhao , Janka Gritta , Henter Jan-Inge 
Published: April 2019

AbstractHemophagocytic lymphohistiocytosis (HLH) is a severe hyperinflammatory syndrome induced by aberrantly activated macrophages and cytotoxic T cells. The primary (genetic) form, caused by mutations affecting lymphocyte cytotoxicity and immune regulation, is most common in children, whereas the secondary (acquired) form is most frequent in adults. Secondary HLH is commonly triggered by infections or malignancies but may also be induced by autoinflammatory/autoimmune disorders, in which case it is called macrophage activation syndrome (MAS; or MAS-HLH). Most information on the diagnosis and treatment of HLH comes from the pediatric literature. Although helpful in some adult cases, this raises several challenges. For example, the HLH-2004 diagnostic criteria developed for children are commonly applied but are not validated for adults. Another challenge in HLH diagnosis is that patients may present with a phenotype indistinguishable from sepsis or multiple organ dysfunction syndrome. Treatment algorithms targeting hyperinflammation are frequently based on pediatric protocols, such as HLH-94 and HLH-2004, which may result in overtreatment and unnecessary toxicity in adults. Therefore, dose reductions, individualized tailoring of treatment duration, and an age-dependent modified diagnostic approach are to be considered. Here, we present expert opinions derived from an interdisciplinary working group on adult HLH, sponsored by the Histiocyte Society, to facilitate knowledge transfer between physicians caring for pediatric and adult patients with HLH, with the aim to improve the outcome for adult patients affected by HLH.
Histamine in psychiatry: promethazine as a sedative anticholinergic
Authors: Cookson John 
Published: April 2019

SUMMARYThe author reflects on discoveries over the course of a century concerning histamine as a potent chemical signal and neurotransmitter, the development of antihistamines, including promethazine, and chlorpromazine from a common precursor, and the recognition of a major brain pathway involving histamine. Although chlorpromazine has been succeeded by numerous other antipsychotics, promethazine remains the antihistamine recommended for sedation in acutely disturbed patients, largely because it is potently anticholinergic at atropinic muscarinic receptors and therefore anti-Parkinsonian: this means it is also useful in combination with older antipsychotics such as haloperidol.DECLARATION OF INTERESTNone.
Leveraging Single-Cell RNA Sequencing Experiments to Model Intratumor Heterogeneity
Authors: Ferrall-Fairbanks Meghan C. , Ball Markus , Padron Eric , Altrock Philipp M. 
Published: April 2019

PURPOSE Many cancers can be treated with targeted therapy. Almost inevitably, tumors develop resistance to targeted therapy, either from pre-existence or by evolving new genotypes and traits. Intratumor heterogeneity serves as a reservoir for resistance, which often occurs as a result of the selection of minor cellular subclones. On the level of gene expression, clonal heterogeneity can only be revealed using high-dimensional single-cell methods. We propose using a general diversity index (GDI) to quantify heterogeneity on multiple scales and relate it to disease evolution. MATERIALS AND METHODS We focused on individual patient samples that were probed with single-cell RNA (scRNA) sequencing to describe heterogeneity. We developed a pipeline to analyze single-cell data via sample normalization, clustering, and mathematical interpretation using a generalized diversity measure, as well as to exemplify the utility of this platform using single-cell data. RESULTS We focused on three sources of patient scRNA sequencing data: two healthy bone marrow (BM) donors, two patients with acute myeloid leukemia—each sampled before and after BM transplantation, four samples of presorted lineages—and six patients with lung carcinoma with multiregion sampling. While healthy/normal samples scored low in diversity overall, GDI further quantified the ways in which these samples differed. Whereas a widely used Shannon diversity index sometimes reveals fewer differences, GDI exhibits differences in the number of potential key drivers or clonal richness. Comparison of pre– and post–BM transplantation acute myeloid leukemia samples did not reveal differences in heterogeneity, although biological differences can exist. CONCLUSION GDI can quantify cellular heterogeneity changes across a wide spectrum, even when standard measures, such as the Shannon index, do not. Our approach can be widely applied to quantify heterogeneity across samples and conditions.
Phthalate Exposure and Breast Cancer Incidence: A Danish Nationwide Cohort Study
Authors: Ahern Thomas P. , Broe Anne , Lash Timothy L. , Cronin-Fenton Deirdre P. , Ulrichsen Sinna Pilgaard , Christiansen Peer M. , Cole Bernard F. , Tamimi Rulla M. , Sørensen Henrik Toft , Damkier Per 
Published: April 2019

PURPOSE Phthalate exposure is ubiquitous and especially high among users of drug products formulated with phthalates. Some phthalates mimic estradiol and may promote breast cancer. Existing epidemiologic studies on this topic are small, mostly not prospective, and have given inconsistent results. We estimated associations between longitudinal phthalate exposures and breast cancer risk in a Danish nationwide cohort, using redeemed prescriptions for phthalate-containing drug products to measure exposure. METHODS We ascertained the phthalate content of drugs marketed in Denmark using an internal Danish Medicines Agency ingredient database. We enrolled a Danish nationwide cohort of 1.12 million women at risk for a first cancer diagnosis on January 1, 2005. By combining drug ingredient data with the Danish National Prescription registry, we characterized annual, cumulative phthalate exposure through redeemed prescriptions. We then fit multivariable Cox regression models to estimate associations between phthalate exposures and incident invasive breast carcinoma according to tumor estrogen receptor status. RESULTS Over 9.99 million woman-years of follow-up, most phthalate exposures were not associated with breast cancer incidence. High-level dibutyl phthalate exposure (≥ 10,000 cumulative mg) was associated with an approximately two-fold increase in the rate of estrogen receptor–positive breast cancer (hazard ratio, 1.9; 95% CI, 1.1 to 3.5), consistent with in vitro evidence for an estrogenic effect of this compound. Lower levels of dibutyl phthalate exposure were not associated with breast cancer incidence. CONCLUSION Our results suggest that women should avoid high-level exposure to dibutyl phthalate, such as through long-term treatment with pharmaceuticals formulated with dibutyl phthalate.
Endometriosis
Authors: Bulun Serdar E , Yilmaz Bahar D , Sison Christia , Miyazaki Kaoru , Bernardi Lia , Liu Shimeng , Kohlmeier Amanda , Yin Ping , Milad Magdy , Wei JianJun 
Published: April 2019

AbstractPelvic endometriosis is a complex syndrome characterized by an estrogen-dependent chronic inflammatory process that affects primarily pelvic tissues, including the ovaries. It is caused when shed endometrial tissue travels retrograde into the lower abdominal cavity. Endometriosis is the most common cause of chronic pelvic pain in women and is associated with infertility. The underlying pathologic mechanisms in the intracavitary endometrium and extrauterine endometriotic tissue involve defectively programmed endometrial mesenchymal progenitor/stem cells. Although endometriotic stromal cells, which compose the bulk of endometriotic lesions, do not carry somatic mutations, they demonstrate specific epigenetic abnormalities that alter expression of key transcription factors. For example, GATA-binding factor-6 overexpression transforms an endometrial stromal cell to an endometriotic phenotype, and steroidogenic factor-1 overexpression causes excessive production of estrogen, which drives inflammation via pathologically high levels of estrogen receptor-β. Progesterone receptor deficiency causes progesterone resistance. Populations of endometrial and endometriotic epithelial cells also harbor multiple cancer driver mutations, such as KRAS, which may be associated with the establishment of pelvic endometriosis or ovarian cancer. It is not known how interactions between epigenomically defective stromal cells and the mutated genes in epithelial cells contribute to the pathogenesis of endometriosis. Endometriosis-associated pelvic pain is managed by suppression of ovulatory menses and estrogen production, cyclooxygenase inhibitors, and surgical removal of pelvic lesions, and in vitro fertilization is frequently used to overcome infertility. Although novel targeted treatments are becoming available, as endometriosis pathophysiology is better understood, preventive approaches such as long-term ovulation suppression may play a critical role in the future.
Measuring and Managing the Externality of Managerial Responses to Online Customer Reviews
Authors: Chen Wei , Gu Bin , Ye Qiang , Zhu Kevin Xiaoguo 
Published: April 2019

Managerial responses to online customer reviews not only affect customers who receive the responses but may also influence subsequent customers who observe the responses. This externality arises because of the public nature of online interactions. However, prior studies were mainly in offline settings where such externality rarely exists. In this study, we assess the magnitude of such externality. Using a difference-in-difference-in-differences framework and matched hotels across two large travel agencies, we find that managerial responses indeed have a significant and positive impact on the volume of subsequent customer reviews. The impact on the review valence is not evident, which can be attributed to the unique design of identity disclosure in our research context. Furthermore, our results suggest nuances that were not known in the prior literature. For example, responding to positive and negative reviews may have different effects on future reviews, and managers should provide detailed responses to negative reviews but brief ones to positive reviews. Our results offer managerial implications to service providers on how to improve customer engagement in the interconnected online environment. The online appendix is available at https://doi.org/10.1287/isre.2018.0781 .
Temporal Changes in Cardiac Troponin I Are Associated with Risk of Cardiovascular Events in the General Population: The Nord-Trøndelag Health Study
Authors: Lyngbakken Magnus N , Røsjø Helge , Holmen Oddgeir L , Dalen Håvard , Hveem Kristian , Omland Torbjørn 
Published: April 2019

Abstract

BACKGROUND
Cardiac troponins are associated with cardiovascular risk in the general population, but whether temporal changes in cardiac troponin I provide independent prognostic information remains uncertain. Using a large community-based cohort with follow-up close to the present day, we aimed to investigate the associations between temporal changes in cardiac troponin and cardiovascular events.

METHODS
We measured cardiac troponin I with a high-sensitivity assay (hs-cTnI) in 4805 participants attending both the second (HUNT 2, 1995–97) and third wave (HUNT 3, 2006–2008) of the prospective observational Nord-Trøndelag Health (HUNT) Study. We constructed statistical models with both relative and absolute changes of hs-cTnI from HUNT 2 to HUNT 3. A composite end point of cardiovascular death or first admission for myocardial infarction or heart failure was generated.

RESULTS
Participants with relative decrease in hs-cTnI were more frequently younger and female and had lower blood pressure and body mass index. Participants with relative increase in hs-cTnI more frequently were older and male, with higher systolic blood pressure. The adjusted hazard ratio (HR) for relative increase in hs-cTnI was 1.68 (95% CI, 1.16–2.42) and the adjusted HR for relative decrease was 1.19 (95% CI, 0.84–1.68). Absolute increases in hs-cTnI exhibited similar prognostic properties as relative increases in hs-cTnI. The most recent measurement of hs-cTnI outperformed the change variables in discrimination and reclassification models.

CONCLUSIONS
Both relative and absolute increases in hs-cTnI are independently associated with cardiovascular risk. For refinement of risk prediction models, the most recent measurement of hs-cTnI should be preferred in clinical practice.
Noncoding RNAs Serve as Diagnosis and Prognosis Biomarkers for Hepatocellular Carcinoma
Authors: Tan Chang , Cao Jingyi , Chen Lu , Xi Xiaochen , Wang Siqi , Zhu Yumin , Yang Liuqing , Ma Longteng , Wang Dong , Yin Jianhua , Zhang Ti , John Lu Zhi 
Published: April 2019

Abstract

BACKGROUND
Reliable noninvasive biomarkers for hepatocellular carcinoma (HCC) diagnosis and prognosis are urgently needed. We explored the potential of not only microRNAs (miRNAs) but other types of noncoding RNAs (ncRNAs) as HCC biomarkers.

METHODS
Peripheral blood samples were collected from 77 individuals; among them, 57 plasma cell-free RNA transcriptomes and 20 exosomal RNA transcriptomes were profiled. Significantly upregulated ncRNAs and published potential HCC biomarkers were validated with reverse transcription (RT)-qPCR in an independent validation cohort (60–150 samples). We particularly investigated the diagnosis and prognosis performance and biological function for 1 ncRNA biomarker, RN7SL1, and its S fragment.

RESULTS
We identified certain circulating ncRNAs escaping from RNase degradation, possibly through binding with RNA-binding proteins: 899 ncRNAs were highly upregulated in HCC patients. Among them, 337 genes were fragmented long noncoding RNAs, 252 genes were small nucleolar RNAs, and 134 genes were piwi-interacting RNAs. Forty-eight candidates were selected and validated with RT-qPCR, of which, 16 ncRNAs were verified to be significantly upregulated in HCC, including RN7SL1, SNHG1, ZFAS1, and LINC01359. Particularly, the abundance of RN7SL1 S fragment discriminated HCC samples from negative controls (area under the curve, 0.87; 95% CI, 0.817–0.920). HCC patients with higher concentrations of RN7SL1 S fragment had lower survival rates. Furthermore, RN7SL1 S fragment alone promoted cancer cell proliferation and clonogenic growth.

CONCLUSIONS
Our results show that various ncRNA species, not only miRNAs, identified in the small RNA sequencing of plasma are also able to serve as noninvasive biomarkers. Particularly, we identified a domain of srpRNA RN7SL1 with reliable clinical performance for HCC diagnosis and prognosis.
A global div-curl-lemma for mixed boundary conditions in weak Lipschitz domains and a corresponding generalized A 0 * \mathrm{A}_{0}^{*} - A 1 \mathrm{A}_{1} -lemma in Hilbert spaces
Authors: Pauly Dirk 
Published: April 2019

Abstract
We prove global and local versions of the so-called

{\operatorname{div}}

-

{\operatorname{curl}}

-lemma,
a crucial result in the homogenization theory of partial differential equations,
for mixed boundary conditions on bounded weak Lipschitz domains in 3D
with weak Lipschitz interfaces.
We will generalize our results using an abstract Hilbert space setting,
which shows corresponding results to hold
in arbitrary dimensions as well as for various differential operators.
The crucial tools and the core of our arguments are Hilbert complexes and related compact embeddings.
The disordered boundary of the cell: emerging properties of membrane-bound intrinsically disordered proteins
Authors: Mohammad Irrem-Laareb , Mateos Borja , Pons Miquel 
Published: April 2019

AbstractWe define the disordered boundary of the cell (DBC) as the system formed by membrane tethered intrinsically disordered protein regions, dynamically coupled to the underlying membrane.The emerging properties of the DBC makes it a global system of study, which cannot be understood from the individual properties of their components. Similarly, the properties of lipid bilayers cannot be understood from just the sum of the properties of individual lipid molecules.The highly anisotropic confined environment, restricting the position and orientation of interacting sites, is affecting the properties of individual disordered proteins. In fact, the collective effect caused by high concentrations of disordered proteins extend beyond the sum of individual effects.Examples of emerging properties of the DBC include enhanced protein-protein interactions, protein-driven phase separations, Z-compartmentalization, and protein modulated electrostatics.
Energy storage analysis of R125 in UIO-66 and MOF-5 nanoparticles: A molecular simulation study
Authors: Wang Qiang , Tang Shengli 
Published: April 2019

AbstractThe efficiency of thermodynamic cycles can be improved by using the optimized working fluid. In the present paper, classic molecular dynamics simulations and grand canonical Monte Carlo were employed to examine the thermal energy storage characteristicsof R125/UIO-66 and R125/MOF-5 nanofluids. The results indicate that the adsorption of R125 in MOF-5 is larger than that in UIO-66. Also, the thermal energy storage capacity of R125 was strengthened by mixing with UIO-66 or MOF-5 nanoparticles. In addition, the R125/UIO-66 mixtures can store less energy than that of R125/MOF-5 mixtures except the temperature difference is 30 K to 50 K.
Cryptanalysis of a hash function, and the modular subset sum problem
Authors: Monico Chris 
Published: April 2019

AbstractRecently, Shpilrain and Sosnovski proposed a hash function based on composition of affine maps.
In this paper, we show that this hash function with its proposed parameters is not
weak collision resistant, for plaintexts of size at least 1.9MB (about {2^{24}} bits).
Our approach is to reduce the preimage problem to a (very) high density instance of the
Random Modular Subset Sum Problem, for which we give an algorithm capable of solving instances of the resulting size.
Specifically, given plaintexts of about 1.9MB, we were able to produce other plaintexts of the same size with the same hash value in about 13 hours each, on average.
An improved version of the AAG cryptographic protocol
Authors: Roman’kov Vitaliĭ 
Published: April 2019

AbstractAn improved version of the Anshel–Anshel–Goldfeld (AAG) algebraic cryptographic key-exchange scheme, that is in particular resistant against the Tsaban linear span cryptanalysis, is established. Unlike the original version, that is based on the intractability of the simultaneous conjugacy search problem for the platform group, the proposed version is based on harder simultaneous membership-conjugacy search problems, and the membership problem needs to be solved for a subset of the platform group that can be easily and efficiently built to be very complicated and without any good structure. A number of other hard problems need to be solved first before start solving the simultaneous membership-conjugacy search problem to obtain the exchanged key.