bluuebunny/crossref_metadata_2025_split huggingface dataset:
Decitabine Response in Breast Cancer Requires Efficient Drug Processing and Is Not Limited by Multidrug Resistance
Authors: Dahn Margaret L. , Cruickshank Brianne M. , Jackson Ainsleigh J. , Dean Cheryl , Holloway Ryan W. , Hall Steven R. , Coyle Krysta M. , Maillet Hillary , Waisman David M. , Goralski Kerry B. , Giacomantonio Carman A. , Weaver Ian C.G. , Marcato Paola 
Published: March 2020

AbstractDysregulation of DNA methylation is an established feature of breast cancers. DNA demethylating therapies like decitabine are proposed for the treatment of triple-negative breast cancers (TNBC) and indicators of response need to be identified. For this purpose, we characterized the effects of decitabine in a panel of 10 breast cancer cell lines and observed a range of sensitivity to decitabine that was not subtype specific. Knockdown of potential key effectors demonstrated the requirement of deoxycytidine kinase (DCK) for decitabine response in breast cancer cells. In treatment-naïve breast tumors, DCK was higher in TNBCs, and DCK levels were sustained or increased post chemotherapy treatment. This suggests that limited DCK levels will not be a barrier to response in patients with TNBC treated with decitabine as a second-line treatment or in a clinical trial. Methylome analysis revealed that genome-wide, region-specific, tumor suppressor gene–specific methylation, and decitabine-induced demethylation did not predict response to decitabine. Gene set enrichment analysis of transcriptome data demonstrated that decitabine induced genes within apoptosis, cell cycle, stress, and immune pathways. Induced genes included those characterized by the viral mimicry response; however, knockdown of key effectors of the pathway did not affect decitabine sensitivity suggesting that breast cancer growth suppression by decitabine is independent of viral mimicry. Finally, taxol-resistant breast cancer cells expressing high levels of multidrug resistance transporter ABCB1 remained sensitive to decitabine, suggesting that the drug could be used as second-line treatment for chemoresistant patients.
Mechanical, Team‐Focused, Video‐Reviewed Cardiopulmonary Resuscitation Improves Return of Spontaneous Circulation After Emergency Department Implementation
Authors: Rolston Daniel M. , Li Timmy , Owens Casey , Haddad Ghania , Palmieri Timothy J. , Blinder Veronika , Wolff Jennifer L. , Cassara Michael , Zhou Qiuping , Becker Lance B. 
Published: March 2020

Background

Outcomes in cardiac arrest remain suboptimal. Mechanical cardiopulmonary resuscitation (
CPR
) has not demonstrated clear clinical benefit; however, video review provides the capability to monitor
CPR
quality and provide constructive feedback to individuals and teams to improve their performance. The aim of our study was to evaluate cardiac arrest outcomes before and after initiation of a mechanical, team‐focused, video‐reviewed CPR intervention.

Methods and Results

In 2018, our emergency department began using mechanical
CPR
; a new team‐focused strategy with nurse‐led Advanced Cardiovascular Life Support; and biweekly, multidisciplinary video review of cardiac arrests. A revised approach to resuscitation was generated from a performance improvement session, and in situ simulation was used to disseminate our approach. The primary outcome of this study was the return of spontaneous circulation rate before and after our mechanical, team‐focused, video‐reviewed CPR intervention. Secondary outcomes included survival to admission and discharge. Multivariable logistic regression modeling was used. The pre‐ and postintervention groups were similar at baseline. A total of 248 patients were included in our study (97 before and 151 after mechanical, team‐focused, video‐reviewed CPR). Return of spontaneous circulation was higher in the intervention group (41% versus 26%;
P
=0.014). There were nonsignificant increases in survival to admission (26% versus 20%;
P
=0.257) and survival to discharge (7% versus 3%;
P
=0.163). After controlling for covariates, the odds of return of spontaneous circulation remained higher after the intervention (odds ratio, 2.11; 95%
CI
, 1.14–3.89).

Conclusions
Implementation of our mechanical, team‐focused, video‐reviewed CPR intervention for cardiac arrest patients in our emergency department improved return of spontaneous circulation rates. Survival to hospital admission and discharge did not improve.
Evaluation of handling, storage, and disposal practices of oral anticancer medications among cancer patients and their caregivers at home setting in the Princess Noorah Oncology Center
Authors: Algethami Ashwag A , Alshamrani Majed A , AlHarbi Atika M , AlAzmi Aeshah A , Khan Mansoor A , AlHadidi Rawad A 
Published: March 2020

Backgroud: Oral medications are commonly prescribed for many cancer patients. Unfortunately, most of them are dispensed without proper counseling about handling practices. We aimed to evaluate the handling, storage, and disposal practices of oral anticancer medications among cancer patients and their caregivers at home. Methods A cross-sectional questionnaire was filled in by adult cancer patients or caregivers who received oral anticancers and/or visited an outpatient pharmacy over two months. Results A total of 201 participants were interviewed, 67% were female, and nearly 44% were between 40 and 60 years of age. The majority of participants were educated (78%). The top five medications involved were: tamoxifen, capecitabine, letrozole, dasatinib, and imatinib. More than 95% of participants reported that medications were kept away from children and pets in the original container and stored away from extreme heat, cold, and humidity. Hand washing and wearing gloves were not consistently practiced. Only 5% reported “Always” wearing gloves, while 24% reported “Always” washing hands after handling anticancer medications. The participants reported that they had been informed about safe handling and storage by their physician (39%) and pharmacist (25%), while 34% had not been informed. In terms of disposal practices, 66% of patients have not had any unused or expired medications, 29% disposed them in the trash, and 27% returned them. Conclusions Our findings suggest that patients and caregivers’ handling practices of oral anticancer medications are inconsistent with the published recommendations. Hence, appropriate and comprehensive education is needed to mitigate the risk of exposure to these agents in the home setting.
New Insights on Psychological Factors for the Development of Women Entrepreneurs in Indonesia
Authors: Riantoputra Corina D. , Muis Ismarli 
Published: March 2020

The Problem Despite efforts to develop women entrepreneurs in Indonesia, the majority of them are unable to grow their businesses. The literature suggests that cultural factors (i.e., non-egalitarian sex roles) may limit the actualization of psychological factors that are critical for their successes. The Solution To investigate the motivation, challenges, and opportunities facing women entrepreneurs in Indonesia, this article focused on (a) characteristics of women entrepreneurs based on their motives: necessity- versus growth-oriented, and (b) psychological factors that influence their success. Focusing on micro and small enterprises, we collected data from 200 (87 necessity-oriented, and 113 growth-oriented) women entrepreneurs in Indonesia. The study findings demonstrate that the success of women entrepreneurs in Indonesia is associated with their identity conflict (i.e., induced by non-egalitarian sex-role culture), passion, and future time orientation, all of which interplay differently for necessity- and growth-oriented women entrepreneurs. The Stakeholders This article is important for scholars, practitioners, and government officers in a non-egalitarian sex-role country like Indonesia. It informs involved stakeholders of the specific aspects that need to be considered in coaching and leadership training for women entrepreneurs who are managing micro and small enterprises.
Exploration of baseline patient-reported side effect bother from cancer therapy
Authors: Roydhouse Jessica K , King-Kallimanis Bellinda L , Roy Pourab , Weinstock Chana , Krol Danielle , Daniels Selena R , Suzman Daniel L , Beaver Julia A , Kluetz Paul G 
Published: March 2020

Background: Patient reports of expected treatment side effects are increasingly collected as part of the assessment of patient experience in clinical trials. A global side effect item that is patient-reported has the potential to inform overall tolerability. Therefore, the aim of this study was to examine the completion and distribution of such a global single-item measure of side effect burden in five cancer clinical trials. Methods: Data from five trials from internal Food and Drug Administration databases that included the Functional Assessment of Cancer Therapy–General single-item measure of overall side effect burden (i.e. impact on degree of bother) were analyzed. Completion rates for the side effect bother item, items adjacent to this item, and two non-adjacent items on the Functional Assessment of Cancer Therapy–General that are related to health-related quality of life were calculated at the baseline assessment and at the 3-month assessment. To evaluate the distribution, the percentage of patients reporting high levels (quite a bit or very much bother) of side effect bother at baseline and 3 months was assessed. Results: Completion rates for all items were at least 80% regardless of time point or trial population. However, in three of the five trials, completion rates for the side effect bother item were lower at baseline compared to adjacent and non-adjacent items. This difference was not observed at 3 months. Up to 9.4% of patients reported high levels of side effect bother at baseline. Conclusion: Patients may enter trials already reporting some bother from side effects. This can make interpretation of results with respect to the investigational agent under study challenging. Patients may skip an item evaluating side effect bother at baseline, suggesting some difficulty with interpretation of what is being asked. Further study of the wording and utility of a baseline side effect bother assessment is warranted.
A Comparison of Patient and Surgeon Expectations of Spine Surgical Outcomes
Authors: Aoude Ahmed , Litowski Madison , Aldebeyan Sultan , Fisher Charles , Hall Hamilton , Manson Neil , Bailey Christopher S. , Ahn Henry , Abraham Edward , Nataraj Andrew , Paquet Jerome , Stratton Alexandra , Christie Sean , Cadotte David , Nicholls Fred , Soroceanu Alex , Rampersaud Y. Raja , Thomas Kenneth C. 
Published: March 2020

Study Design: Ambispective cohort study. Objective: Limited data exists comparing surgeon and patient expectations of outcome following spine surgery. The objective of this study was to elicit whether any differences exist between patient and surgeon expectations for common spine surgeries. Methods: Ten common age-appropriate clinical scenarios were generated and sent to Canadian spine surgeons to determine surgeon expectations for standard spine surgeries. Patients in the Canadian Spine Outcomes and Research Network (CSORN) registry matching the clinical scenarios were identified. Aggregated patient expectations were compared with surgeon responses for each scenario. A χ2 analysis was then completed to determine discrepancies between surgeon and patient expectations for each scenario. Results: A total of 51 Canadian spine surgeons completed the survey on surgical expectations. A total of 919 patients from multiple centers were identified within the CSORN database that matched the clinical scenarios. Our results demonstrated that patients tend to be more optimistic about the expected outcomes of surgery compared with the treating surgeon. The majority of patients in all clinical scenarios anticipated improvement in back or neck pain after surgery, which differed from surgeon expectations. Results also highlighted the effect of patient age on both patient and surgeon expectations. Discrepancies between patient and surgeon expectations were higher for older patients. Conclusion: We present data on patient and surgeon expectations for spine surgeries and show that differences exist particularly concerning the improvement of neck or back pain. Patient age plays a role in the agreement between the treating physicians and patients in regard to surgical expectations. The reasons for the discrepancies remain unclear.
Tracing CLL-biased stereotyped immunoglobulin gene rearrangements in normal B cell subsets using a high-throughput immunogenetic approach
Authors: Colombo Monica , Bagnara Davide , Reverberi Daniele , Matis Serena , Cardillo Martina , Massara Rosanna , Mastracci Luca , Ravetti Jean Louis , Agnelli Luca , Neri Antonino , Mazzocco Michela , Squillario Margherita , Mazzarello Andrea Nicola , Cutrona Giovanna , Agathangelidis Andreas , Stamatopoulos Kostas , Ferrarini Manlio , Fais Franco 
Published: March 2020

Abstract
Background
B cell receptor Immunoglobulin (BcR IG) repertoire of Chronic Lymphocytic Leukemia (CLL) is characterized by the expression of quasi-identical BcR IG. These are observed in approximately 30% of patients, defined as stereotyped receptors and subdivided into subsets based on specific VH CDR3 aa motifs and phylogenetically related IGHV genes. Although relevant to CLL ontogeny, the distribution of CLL-biased stereotyped immunoglobulin rearrangements (CBS-IG) in normal B cells has not been so far specifically addressed using modern sequencing technologies. Here, we have investigated the presence of CBS-IG in splenic B cell subpopulations (s-BCS) and in CD5+ and CD5− B cells from the spleen and peripheral blood (PB).

Methods
Fractionation of splenic B cells into 9 different B cell subsets and that of spleen and PB into CD5+ and CD5− cells were carried out by FACS sorting. cDNA sequences of BcR IG gene rearrangements were obtained by NGS. Identification of amino acidic motifs typical of CLL stereotyped subsets was carried out on IGHV1-carrying gene sequences and statistical evaluation has been subsequently performed to assess stereotypes distribution.

Results
CBS-IG represented the 0.26% average of IGHV1 genes expressing sequences, were detected in all of the BCS investigated. CBS-IG were more abundant in splenic and circulating CD5+ B (0.57%) cells compared to CD5− B cells (0.17%). In all instances, most CBS IG did not exhibit somatic hypermutation similar to CLL stereotyped receptors. However, compared to CLL, they exhibited a different CLL subset distribution and a broader utilization of the genes of the IGHV1 family.

Conclusions
CBS-IG receptors appear to represent a part of the “public” BcR repertoire in normal B cells. This repertoire is observed in all BCS excluding the hypothesis that CLL stereotyped BcR accumulate in a specific B cell subset, potentially capable of originating a leukemic clone. The different relative representation of CBS-IG in normal B cell subgroups suggests the requirement for additional selective processes before a full transformation into CLL is achieved.
Slower, shorter, sadder: a qualitative study exploring how dog walks change when the canine participant develops osteoarthritis
Authors: Belshaw Zoe , Dean Rachel , Asher Lucy 
Published: March 2020

Abstract
Background
Dog walking may have multiple physical and mental health advantages, but not all dog owners appear to benefit. Dog health is a described barrier to dog walking activity, but specific causes and impacts of reduced exercise in owners of dogs with health problems have not previously been reported. The current study used a qualitative methodology to explore the impact of canine osteoarthritis on dog walking activity.

Methods
Owners of dogs with osteoarthritis living in the United Kingdom (UK) were recruited through veterinary practices for semi-structured interview about life with an osteoarthritic dog. Participants were asked to reflect on walks that they had taken with their dog before he/she developed osteoarthritis, and to describe how those walks had changed. Interviews were transcribed verbatim and thematic analysis was used to construct key themes.

Results
Forty owners of 35 osteoarthritic dogs were interviewed. Prior to their dog’s development of osteoarthritis, dog walking distance, speed and location were usually decided by the owner to satisfy the needs and enjoyment of dog and walker. A diagnosis of canine osteoarthritis led to both dogs and their owners altering the walks undertaken. Walks were typically slower, shorter and limited to locations where physical infrastructure, underfoot surface and gradients were perceived by the owner to be navigable by their dog. Most owners did not go on additional walks without their dog due to feelings of guilt and because walking without a dog was less enjoyable. Many owners described negative effects on their own physical health and diminished enjoyment of walking as a result of their dog’s condition.

Conclusion
Our research suggests that osteoarthritic dogs may reduce the walking exercise their owners are able or willing to undertake. Since osteoarthritis is a common condition in older dogs, this is an important finding for those advocating dog ownership as a positive public health intervention. Strategies may be needed to ensure that owners of dogs that develop physical incapacities can continue to enjoy the health benefits they previously associated with dog walking. Future studies investigating dog walking activity should ensure that the health status of the dog has been considered.
Ascarid infection in wild Amur tigers (Panthera tigris altaica) in China
Authors: Peng Zhi-wei , Ning Yao , Liu Dan , Sun Ying , Wang Li-xin , Zhai Qi-an , Hou Zhi-jun , Chai Hong-liang , Jiang Guang-shun 
Published: March 2020

AbstractBackgroundWild Amur tigers are a sparsely populated species, and the conservation of this species is of great concern worldwide, but as an important health risk factor, parasite infection in them is not fully understanding.ResultsIn this study, sixty-two faecal samples were collected to investigate the frequency and infection intensity ofToxocara catiandToxascaris leoninain wild Amur tigers. TheT. catiandT. leoninaeggs were preliminary identified by microscopy, and confirmed by molecular techniques. Infection intensity was determined by the modified McMaster technique. Phylogenetic trees demonstrated thatT. catiof wild Amur tiger had a closer relationship with which of other wild felines than that of domestic cats.T. leoninaof Amur tiger and other felines clustered into one clade, showing a closer relationship than canines. The average frequency ofT. catiwas 77.42% (48/62), and the frequency in 2016 (100%) were higher than those in 2013 (P = 0.051, < 0.1; 66.6%) and 2014 (P = 0.079, < 0.1; 72.2%). The infection intensity ofT. catiranged from 316.6 n/g to 1084.1 n/g. ForT. leonina, only three samples presented eggs when the saturated sodium chloride floating method was performed, indicating that the frequency is 4.83% (3/62). Unfortunately, the egg number in faecal smears is lower than the detective limitation, so the infection intensity ofT. leoninais missed.ConclusionsThis study demonstrated that ascarids are broadly prevalent, andT. catiis a dominant parasite species in the wild Amur tiger population.
Glycemic status and risks of thromboembolism and major bleeding in patients with atrial fibrillation
Authors: Chan Yi-Hsin , Chuang Chi , Chan Cze-Ci , Lee Hsin-Fu , Huang Ya-Chi , Huang Yu-Tung , Chang Shang-Hung , Wang Chun-Li , Chao Tze-Fan , Kuo Chi-Tai , Yeh Yung-Hsin , Chen Shih-Ann 
Published: March 2020

AbstractBackgroundStudies specifically examining the association between glycated hemoglobin A1c (HbA1c) levels and ischemic stroke/systemic thromboembolism (IS/SE) risk in atrial fibrillation (AF) patients are limited. Here, we investigated the association between HbA1c levels and the risk of IS/SE, as well as major bleeding, among AF patients with or without oral anticoagulants (OACs). We also compared the effectiveness and safety of warfarin and direct oral anticoagulants (DOACs) in different HbA1c categories.MethodsWe utilized medical data from a multi-center healthcare provider in Taiwan, which included 34,036 AF patients with serum HbA1c data available within 3 months after AF being diagnosed. Patients were divided into seven study groups according to their HbA1c levels: < 5.4%, 5.4%–5.6%, 5.7%–5.9%, 6.0%–6.4%, 6.5%–6.9%, 7.0%–7.9%, and ≥ 8.0%. The risks of IS/SE and major bleeding were compared among the groups after adjusting for baseline stroke and bleeding risk factors.ResultsCompared with the patients with HbA1c level < 5.4%, IS/SE risk significantly increased at HbA1c levels higher than 6.5% [adjusted hazard ratio (HR): 1.20, 95% confidence interval (CI): 1.00–1.43 for HbA1c level 6.5%–6.9%; 1.32, (95% CI 1.11–1.57) for HbA1c level 7.0%–7.9%; and 1.48 (95% CI 1.25–1.76) for HbA1c level ≥ 8.0%]. These results were generally consistent in AF patients without OACs (n = 24,931). However, among 9105 patients receiving OACs, IS/SE risk was not higher for patients having higher HbA1c levels. The risk of major bleeding was comparable across all HbA1c categories. Compared with warfarin, DOACs were associated with lower risks of IS/SE (adjusted HR: 0.61, 95% CI 0.49–0.75) and major bleeding (adjusted HR: 0.30, 95% CI 0.21–0.42) without interactions across different HbA1c categories (allPinteractions > 0.05).ConclusionFor AF patients, IS/SE risk significantly increased once HbA1c levels exceeded 6.5%, and OACs may attenuate these associations. Compared with warfarin, DOACs were more effective and safer across broad HbA1c categories. Therefore, in addition to prescribing DOACs when indicated, more aggressive glycemic control to achieve an HbA1c level < 6.5% may be considered for eligible AF patients and should be tested in further prospective studies.
Toll signaling promotes JNK-dependent apoptosis in Drosophila
Authors: Li Zhuojie , Wu Chenxi , Ding Xiang , Li Wenzhe , Xue Lei 
Published: March 2020

AbstractBackgroundApoptosis plays pivotal roles in organ development and tissue homeostasis, with its major function to remove unhealthy cells that may compromise the fitness of the organism. Toll signaling, with the ancient evolutionary origin, regulates embryonic dorsal–ventral patterning, axon targeting and degeneration, and innate immunity. UsingDrosophilaas a genetic model, we characterized the role of Toll signaling in apoptotic cell death.ResultsWe found that gain of Toll signaling is able to trigger caspase-dependent cell death in development. In addition, JNK activity is required for Toll-induced cell death. Furthermore, ectopic Toll expression induces the activation of JNK pathway. Moreover, physiological activation of Toll signaling is sufficient to produce JNK-dependent cell death. Finally, Toll signaling activates JNK-mediated cell death through promoting ROS production.ConclusionsAs Toll pathway has been evolutionarily conserved fromDrosophilato human, this study may shed light on the mechanism of mammalian Toll-like receptors (TLRs) signaling in apoptotic cell death.