bluuebunny/crossref_metadata_2025_split huggingface dataset:
How to improve the concept of individualised antiplatelet therapy with P2Y12 receptor inhibitors – is an algorithm the answer?
Authors: Trenk Dietmar , Schrör Karsten , Gawaz Meinrad , Kristensen Steen D. , Storey Robert F. , Huber Kurt , Siller-Matula Jolanta M. ,   for the European Platelet Academy
Published: September 2014

SummaryWithin the past decade, high on-treatment platelet reactivity (HTPR) on clopidogrel and its clinical implications have been frequently discussed. Although it has been previously assumed that HTPR is a phenomenon occurring only in patients treated with clopidogrel, recent data show that HTPR might also occur during treatment with prasugrel or ticagrelor in the acute phase of ST-elevation myocardial infarction. Moreover, it has been postulated that there is a therapeutic window for P2Y12 receptor blockers, thus indicating that HTPR is associated with thrombotic events whereas low on-treatment platelet reactivity (LTPR) is associated with bleeding events. The current paper focuses on tools to identify risk factors for HTPR (pharmacogenomic testing, clinical scoring and drug-drug interactions) and on the use of platelet function testing in order to identify patients who might not respond adequately to clopidogrel. The majority of recent clinical randomised trials have not supported the hypothesis that platelet function testing and tailored antiplatelet therapy are providing a favourable clinical outcome. These trials, mainly performed in low-to-moderate risk patients, will be reviewed and discussed. Finally, an algorithm based on current knowledge is suggested, which might be of use for design of clinical trials.
Vacuum-assisted breast biopsy with 7-gauge, 8-gauge, 9-gauge, 10-gauge, and 11-gauge needles: how many specimens are necessary?
Authors: Preibsch Heike , Baur Astrid , Wietek Beate M , Krämer Bernhard , Staebler Annette , Claussen Claus D , Siegmann-Luz Katja C 
Published: September 2014

Background Published national and international guidelines and consensus meetings on the use of vacuum-assisted biopsy (VAB) give different recommendations regarding the required numbers of tissue specimens depending on needle size and imaging method. Purpose To evaluate the weights of specimens obtained with different VAB needles to facilitate the translation of the required number of specimens between different breast biopsy systems and needle sizes, respectively. Material and Methods Five different VAB systems and seven different needle sizes were used: Mammotome® (11-gauge (G), 8-G), Vacora® (10-G), ATEC Sapphire™ (9-G), 8-G Mammotome® Revolve™, and EnCor Enspire® (10-G, 7-G). We took 24 (11-G) or 20 (7–10-G) tissue cores from a turkey breast phantom. The mean weight of a single tissue core was calculated for each needle size. A matrix, which allows the translation of the required number of tissue cores for different needle sizes, was generated. Results were compared to the true cumulative tissue weights of consecutively harvested tissue cores. Results The mean tissue weights obtained with the 11-G / 10-G Vacora® / 10-G Enspire® / 9-G / 8-G Original / 8-G Revolve™ / 7-G needles were 0.084 g / 0.142 g / 0.221 g / 0.121 g / 0.192 g / 0.334 g / 0.363 g, respectively. The calculated required numbers of VAB tissue cores for each needle size build the matrix. For example, the minimum calculated number of required cores according to the current German S3 guideline is 20 / 12 / 8 / 14 / 9 / 5 / 5 for needles of 11-G / 10-G Vacora® / 10-G Enspire® / 9-G / 8-G Original / 8-G Revolve™ / 7-G size. These numbers agree with the true cumulative tissue weights. Conclusion The presented matrix facilitates the translation of the required number of VAB specimens between different needle sizes and thereby eases the implementation of current guidelines and consensus recommendations into clinical practice.
Ubiquinol Reduces Muscle Wasting but Not Fatigue in Tumor-Bearing Mice
Authors: Clark Yvonne Y. , Wold Loren E. , Szalacha Laura A. , McCarthy Donna O. 
Published: September 2014

Purpose: Fatigue is the most common and distressing symptom reported by cancer patients during and after treatment. Tumor growth increases oxidative stress and cytokine production, which causes skeletal muscle wasting and cardiac dysfunction. The purpose of this study was to determine whether treatment with the antioxidant ubiquinol improves muscle mass, cardiac function, and behavioral measures of fatigue in tumor-bearing mice. Method: Adult female mice were inoculated with colon26 tumor cells. Half the control and tumor-bearing mice were administered ubiquinol (500 mg/kg/day) in their drinking water. Voluntary wheel running (i.e., voluntary running activity [VRA]) and grip strength were measured at Days 0, 8, 14, and 17 of tumor growth. Cardiac function was measured using echocardiography on Day 18 or 19. Biomarkers of inflammation, protein degradation, and oxidative stress were measured in serum and heart and gastrocnemius tissue. Results: VRA and grip strength progressively declined in tumor-bearing mice. Muscle mass and myocardial diastolic function were decreased, and expression of proinflammatory cytokines was increased in serum and muscle and heart tissue on Day 19 of tumor growth. Oxidative stress was present only in the heart, while biomarkers of protein degradation were increased only in the gastrocnemius muscle. Ubiquinol increased muscle mass in the tumor-bearing and control animals but had no effect on the expression of biomarkers of inflammation, protein degradation, or oxidative stress or on behavioral measures of fatigue.
Antihyperglycaemic therapies and cancer risk
Authors: Lutz Stefan Z , Staiger Harald , Fritsche Andreas , Häring Hans-Ulrich 
Published: September 2014

Aims: This review is aimed at highlighting the potential mitogenic/tumour growth–promoting or antimitogenic/tumour growth–inhibiting effects of the main antihyperglycaemic drug classes. Methods: We review and discuss the most current studies evaluating the association between antidiabetic medications used in clinical practice and malignancies as described so far. Results: Metformin seems to be the only antidiabetic drug to exert protective effects both on monotherapy and also when combined with other oral antidiabetic drugs or insulins in several site-specific cancers. In contrast, several other drug classes may increase cancer risk. Some reason for concern remains regarding sulphonylureas and also the incretin-based therapies regarding pancreas and thyroid cancers and the sodium glucose cotransporter-2 inhibitors as well as pioglitazone regarding bladder cancer. The majority of meta-analyses suggest that there is no evidence for a causal relationship between insulin glargine and elevated cancer risk, although the studies have been controversially discussed. For α-glucosidase inhibitors and glinides, neutral or only few data upon cancer risk exist. Conclusion: Although the molecular mechanisms are not fully understood, a potential risk of mitogenicity and tumour growth promotion cannot be excluded in case of several antidiabetic drug classes. However, more large-scale, randomized, well-designed clinical studies with especially long follow-up time periods are needed to get reliable answers to these safety issues.
Senescence and apoptosis block hematopoietic activation of quiescent hematopoietic stem cells with short telomeres
Authors: Wang Jianwei , Lu Xin , Sakk Vadim , Klein Christoph A. , Rudolph Karl Lenhard 
Published: September 2014

Key Points
DNA damage induced by telomere shortening resides in most quiescent HSCs. Senescence and apoptosis compromise the activation of HSCs with dysfunctional telomeres.
How I treat myelofibrosis
Authors: Cervantes Francisco 
Published: September 2014

Abstract
Myelofibrosis (MF) is a BCR-ABL1–negative myeloproliferative neoplasm characterized by clonal myeloproliferation, dysregulated kinase signaling, and release of abnormal cytokines. In recent years, important progress has been made in the knowledge of the molecular biology and the prognostic assessment of MF. Conventional treatment has limited impact on the patients’ survival; it includes a wait-and-see approach for asymptomatic patients, erythropoiesis-stimulating agents, androgens, or immunomodulatory agents for anemia, cytoreductive drugs such as hydroxyurea for the splenomegaly and constitutional symptoms, and splenectomy or radiotherapy in selected patients. The discovery of the Janus kinase (JAK)2 mutation triggered the development of molecular targeted therapy of MF. The JAK inhibitors are effective in both JAK2-positive and JAK2-negative MF; one of them, ruxolitinib, is the current best available therapy for MF splenomegaly and constitutional symptoms. However, although ruxolitinib has changed the therapeutic scenario of MF, there is no clear indication of a disease-modifying effect. Allogeneic stem cell transplantation remains the only curative therapy of MF, but due to its associated morbidity and mortality, it is usually restricted to eligible high- and intermediate-2–risk MF patients. To improve current therapeutic results, the combination of JAK inhibitors with other agents is currently being tested, and newer drugs are being investigated.
Should we consider the infusion of lipid emulsion in the resuscitation of poisoned patients?
Authors: Cave Grant , Harvey Martyn G 
Published: September 2014

AbstractThe use of intravenous lipid emulsions (ILEs) as antidote in local anaesthetic systemic toxicity has gained widespread support following convincing data from animal models, and successful case reports in humans. Proposed beneficial mechanisms of action for ILEs include intravascular sequestration of intoxicant and subsequent enhanced redistribution to biologically inert tissues, augmentation of fatty acid utilisation for ATP synthesis in the context of metabolic poisoning, and direct cardiotonic and ion channel effects. The evidence base for use of ILEs in acute drug intoxication is evolving. The present evidence supports use of ILEs only in local anaesthetic systemic toxicity and in lipophilic cardiotoxin intoxication when there is an immediate threat to life, and other therapies have proven ineffective.
Integrative Analysis of mRNA and miRNA Array Data Reveals the Suppression of Retinoic Acid Pathway in Regulatory T Cells of Graves' Disease
Authors: Wang Zhe , Fan Xiaohua , Zhang Rongrong , Lin Zongwei , Lu Ting , Bai Xue , Li Wenchao , Zhao Jiajun , Zhang Qunye 
Published: September 2014

Context:
It is well known that regulatory T cells (Tregs) are abnormal in Graves' disease (GD) and play crucial roles in the breakdown of immune tolerance and GD development. However, there are controversies about whether the quantity and/or function of Tregs is aberrant in GD. The molecular mechanism of Tregs abnormality and its effects on GD development was still unclear, until now.

Objective:
MiRNAs play important roles in the function and development of the immune system including Tregs. To reveal the Tregs abnormality and its molecular mechanism in GD, we systematically studied the quantity and immunosuppressive function as well as the differential expression profiles of miRNA and mRNA of Tregs in newly diagnosed patients with GD using TaqMan miRNA array and mRNA microarray.

Results:
Our results showed that the quantity and immunosuppressive function of Tregs in initial patients with GD was significantly decreased. More importantly, the retinoic acid (RA) pathway was markedly suppressed and its agonist, all-trans retinoic acid, could notably improve the quantity and immunosuppressive function of Tregs from patients with GD in vitro. In addition, many other pathways including protein ubiquitination and circadian rhythm were also significantly regulated in Tregs of GD.

Conclusions:
This integrative study first revealed the expression profiles of mRNA/miRNA in Tregs of initial GD and RA pathway might play important roles in GD development. Our results implied that all-trans RA, which had been used for a long time in the clinical setting, had potential value in the treatment of GD and was worthy of additional study.
Decimal Commas Are a Problem; Actiq Is Not for Sore Throats; Dosing Error with Tasigna; Repackaging of Imbruvica Is Approved
Authors: Cohen Michael R. , Smetzer Judy L. 
Published: September 2014

These medication errors have occurred in health care facilities at least once. They will happen again—perhaps where you work. Through education and alertness of personnel and procedural safeguards, they can be avoided. You should consider publishing accounts of errors in your newsletters and/or presenting them at your inservice training programs. Your assistance is required to continue this feature. The reports described here were received through the Institute for Safe Medication Practices (ISMP) Medication Errors Reporting Program. Any reports published by ISMP will be anonymous. Comments are also invited; the writers’ names will be published if desired. ISMP may be contacted at the address shown below. Errors, close calls, or hazardous conditions may be reported directly to ISMP through the ISMP Web site ( www.ismp.org ), by calling 800-FAIL-SAFE, or via e-mail at ismpinfo@ismp.org . ISMP guarantees the confidentiality and security of the information received and respects reporters’ wishes as to the level of detail included in publications.
Significant Publications for Pharmacy Nutrition Support Practice in 2013
Authors: Dickerson Roland N. , Kumpf Vanessa J. , Rollins Carol J. , Frankel Eric H. , Kraft Michael D. , Canada Todd W. , Crill Catherine M. 
Published: September 2014

Purpose To assist the pharmacy clinician engaged in nutrition support in staying current with the most pertinent literature. Methods Several experienced board-certified clinical pharmacists in nutrition support compiled a list of publications published in 2013 that they considered to be important to their practice. The citation list was compiled into a Web-based survey whereby pharmacist members of the American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.), GI-Liver-Nutrition Practice Research Network of the American College of Clinical Pharmacy, and the Pharmacy and Pharmacology Section of the Society of Critical Care Medicine were asked to rank each article according to level of importance in their practice. Results A total of 30 articles were identified by the author group. Thirty-six participants responded to the survey. The top-ranked papers by participants from the Web-based survey were reviewed by the authors. Due to its high level of importance, the parenteral nutrition safety consensus recommendations article, to be published in 2014 by A.S.P.E.N., was also reviewed. Conclusion It is recommended that the informed pharmacist, who is engaged in nutrition support therapy, be familiar with the majority of these publications.
Estimated Cost Savings from Reducing Errors in the Preparation of Sterile Doses of Medications
Authors: Urbine Terry F. , Schneider Philip J. 
Published: September 2014

Background Preventing intravenous (IV) preparation errors will improve patient safety and reduce costs by an unknown amount. Objective To estimate the financial benefit of robotic preparation of sterile medication doses compared to traditional manual preparation techniques. Methods A probability pathway model based on published rates of errors in the preparation of sterile doses of medications was developed. Literature reports of adverse events were used to project the array of medical outcomes that might result from these errors. These parameters were used as inputs to a customized simulation model that generated a distribution of possible outcomes, their probability, and associated costs. Results By varying the important parameters across ranges found in published studies, the simulation model produced a range of outcomes for all likely possibilities. Thus it provided a reliable projection of the errors avoided and the cost savings of an automated sterile preparation technology. The average of 1,000 simulations resulted in the prevention of 5,420 medication errors and associated savings of $288,350 per year. The simulation results can be narrowed to specific scenarios by fixing model parameters that are known and allowing the unknown parameters to range across values found in previously published studies. Conclusions The use of a robotic device can reduce health care costs by preventing errors that can cause adverse drug events.
Recurrent Venous Thromboembolism in a Patient with Heterozygous Factor V Leiden Mutation
Authors: White C. Whitney , Thomason Angela R. , Prince Valerie 
Published: September 2014

Objective To report a patient case identifying risk for recurrent venous thromboembolism (VTE) associated with heterozygous Factor V Leiden mutation. Case Summary A 54-year-old Caucasian male was diagnosed with heterozygous Factor V Leiden mutation in 2008 after experiencing a deep vein thrombosis (DVT) and bilateral pulmonary embolism. The patient was treated appropriately and started on anticoagulation therapy with warfarin through an anticoagulation management clinic. After approximately 17 months of warfarin therapy without incident, warfarin was discontinued. Within 2 months after discontinuation of anticoagulation therapy, the patient experienced his second DVT and left pulmonary artery embolus. Discussion The risk of recurrent venous thromboembolism (VTE) in patients with heterozygous Factor V Leiden mutation is documented as an approximate 1.4-fold increase compared to patients without thrombophilia. However, the risk increases dramatically when nonreversible (age) or reversible risk factors (obesity, smoking, and long air flights) are present in this population. Conclusion Based on recent literature, heterozygous Factor V Leiden mutation exponentially increases the risk of recurrent VTE, especially in the presence of other risk factors. Health care providers should complete a comprehensive review of the patients’ other risk factors when deciding on duration of anticoagulation therapy for patients with positive heterozygous Factor V Leiden mutation.
Serrin's over-determined problem on Riemannian manifolds
Authors: Fall Mouhamed Moustapha , Minlend Ignace Aristide 
Published: September 2014

Abstract
Let

(
ℳ
,
g
)

${(\mathcal {M},g)}$

be a compact Riemannian manifold of
dimension N, N ≥ 2. In this paper, we prove that there exists
a family of domains

(

Ω
ε

)

ε
∈
(
0
,

ε
0

)

${(\Omega _\varepsilon )_{\varepsilon \in (0,\varepsilon _0)}}$

and functions

u
ε

${u_\varepsilon }$

such that

-

Δ
g

u
ε

=
1

$-\Delta _{g} u_\varepsilon =1$

in

Ω
ε

$\Omega _\varepsilon $

,

u
ε

=
0

$u_\varepsilon =0$

on

∂

Ω
ε

$\partial \Omega _\varepsilon $

,

g

(

∇
g

u
ε

,

ν
ε

)

=
-

ε
N

${g}(\nabla _{ {g}} {u_\varepsilon }, {\nu }_\varepsilon )=-\frac{\varepsilon }{N}$

on

∂

Ω
ε

$\partial \Omega _\varepsilon $

,
where

ν
ε

${\nu _\varepsilon }$

is the unit outer normal of

∂

Ω
ε

${\partial \Omega _\varepsilon }$

.
The domains

Ω
ε

${\Omega _\varepsilon }$

are smooth perturbations of geodesic balls of radius ε. If, in addition,
p
0 is a non-degenerate critical point of the scalar curvature of
g, then the family

(
∂

Ω
ε

)

ε
∈
(
0
,

ε
0

)

${(\partial \Omega _\varepsilon )_{\varepsilon \in (0,\varepsilon _0)}}$

constitutes a
smooth foliation of a neighborhood of p
0. By considering a family of domains

Ω
ε

${\Omega _\varepsilon }$

in which the above problem is satisfied, we also prove that if this family
converges to some point p
0 in a suitable sense as

ε
→
0

${\varepsilon \rightarrow 0}$

, then p
0 is a critical point of the scalar curvature.
A Taylor expansion of the energy rigidity for the torsion problem is also given.
Oxidation of High Titanium Slag through Microwave Treatment
Authors: Yang Kun , Zhang Libo , Peng Jinhui , Zhu Hongbo , Chen Guo , Zhang Shimin 
Published: September 2014

AbstractDue to its special nature of microwave heating, the reaction processes of high dielectric loss materials under microwave field draw more and more attention. This work attempts to figure out microwave oxidation process of high titanium slag. Based on a through analysis, it can be concluded that high titanium slag phase transformation process under microwave field can be divided into four stages: (i) crystallization of amorphous Fe, Mg, and Ti oxides, (ii) decomposition of Fe
Simplified Calculation Kinetic Model for Solid Metal Melting and Decarburization Process
Authors: Dong Kai , Zhu Rong , Liu Wenjuan 
Published: September 2014

AbstractIn this paper, a calculation model for decarburization kinetic in solid metal melting process is studied. Firstly the macro-kinetic model is established, and the melting and decarburization process is divided into five steps, which are adsorption and dissolution of O
Theory of Doping in Studies of Defect Concentration and Transport Properties of Transition Metal Oxides and Sulphides
Authors: Grzesik Zbigniew 
Published: September 2014

AbstractIn the present paper the theoretical basis and experimental verification of a method, enabling the calculation of defect concentration and their mobility in transition metal oxides and sulphides have been described. The idea of proposed method consists in determination of both these parameters in indirect way, i.e. in studying the influence of aliovalent metallic additions on the oxidation kinetics of a given metal (doping effect). It has been shown that from the results of oxidation kinetics of binary alloys, the enthalpy and entropy of defect formation and their migration can be calculated. These data, in turn, can be used for the calculation of defect concentration and defect mobility in pure, undoped oxides. Such a possibility has been illustrated on the example of nonstoichiometric nickel oxide, Ni
Too Many Nonprofits? An Empirical Approach to Estimating Trends in Nonprofit Demand Density
Authors: Harrison Teresa , Thornton Jeremy 
Published: September 2014

AbstractWe examine the claim that nonprofit markets have become more crowded over time. A naïve examination of the data indicates that the number of nonprofits has increased rapidly over the past two decades. However, this approach does not account for increases in population, income, or other demand factors that would alter a population’s ability to support additional nonprofits. We attempt to quantify a standard unit of demand for nonprofits over time, by exploiting the panel nature of our data. Our findings indicate that nonprofit density, normalized for changes in demand, in 2005 is lower than it was in 1990. We are also able to examine the impact of incremental increases in population to absorb a nonprofit. Overall, we find that it takes far more people to support nonprofit entry in 2005 compared to 1990. It is likely that technological shifts in production and management techniques introduced since 1990 allow firms to serve larger numbers of people. Consistent with our findings, this type of change would result in fewer nonprofits per market, serving larger numbers of people. Our results therefore provide evidence that growth in the nonprofit sector has not necessarily implied increased density or greater competition in the sector.
Liberal and Radical Democracies: The Swiss Cantons Compared
Authors: Bühlmann Marc , Vatter Adrian , Dlabac Oliver , Schaub Hans-Peter 
Published: September 2014

AbstractThis article examines the widespread hypothesis that German-speaking Swiss cantons exhibit radical-democratic characteristics, while the Latin cantons possess stronger liberal-representative democratic profiles. Empirical and multi-dimensional measuring of the quality of democracy in the cantons shows that this hypothesis does not do the complexity of cantonal democracy justice. Today’s position of the cantons along the axes of liberal and radical democracy is best explained with reference to the strong liberal and democratic constitutional movements within the cantons during the middle of the 19th century.