bluuebunny/crossref_metadata_2025_split huggingface dataset:
Measurement of ex vivo resistance to proteasome inhibitors, IMiDs, and daratumumab during multiple myeloma progression
Authors: Walker Zachary J. , VanWyngarden Michael J. , Stevens Brett M. , Abbott Diana , Hammes Andrew , Langouët-Astrie Christophe , Smith Clayton A. , Palmer Brent E. , Forsberg Peter A. , Mark Tomer M. , Jordan Craig T. , Sherbenou Daniel W. 
Published: April 2020

Abstract
The oncogenic drivers and progression factors in multiple myeloma (MM) are heterogeneous and difficult to target therapeutically. Many different MM drugs have emerged, however, that attack various phenotypic aspects of malignant plasma cells. These drugs are administered in numerous, seemingly interchangeable combinations. Although the availability of many treatment options is useful, no clinical test capable of optimizing and sequencing the treatment regimens for an individual patient is currently available. To overcome this problem, we developed a functional ex vivo approach to measure patients’ inherent and acquired drug resistance. This method, which we termed myeloma drug sensitivity testing (My-DST), uses unselected bone marrow mononuclear cells with a panel of drugs in clinical use, followed by flow cytometry to measure myeloma-specific cytotoxicity. We found that using whole bone marrow cultures helped preserve primary MM cell viability. My-DST was used to profile 55 primary samples at diagnosis or at relapse. Sensitivity or resistance to each drug was determined from the change in MM viability relative to untreated control samples. My-DST identified progressive loss of sensitivity to immunomodulatory drugs, proteasome inhibitors, and daratumumab through the disease course, mirroring the clinical development of resistance. Prospectively, patients’ ex vivo drug sensitivity to the drugs subsequently received was sensitive and specific for clinical response. In addition, treatment with &lt;2 drugs identified as sensitive by My-DST led to inferior depth and duration of clinical response. In summary, ex vivo drug sensitivity is prognostically impactful and, with further validation, may facilitate more personalized and effective therapeutic regimens.
CpG methylation in cell-free Epstein-Barr virus DNA in patients with EBV-Hodgkin lymphoma
Authors: Shamay Meir , Kanakry Jennifer A. , Low John S. W. , Horowitz Netanel A. , Journo Guy , Ahuja Anuj , Eran Yonatan , Barzilai Elinor , Dann Eldad J. , Stone Jennifer , Woo Wan Lu , Hsieh Wen-son , Xian Rena R. , Ambinder Richard F. 
Published: April 2020

Abstract
Epstein-Barr virus (EBV) is associated with a variety of tumors and nonmalignant conditions. Latent EBV genomes in cells, including tumor cells, are often CpG methylated, whereas virion DNA is not CpG methylated. We demonstrate that methyl CpG binding magnetic beads can be used to fractionate among sources of EBV DNA (DNA extracted from laboratory-purified virions vs DNA extracted from latently infected cell lines). We then applied the technique to plasma specimens and showed that this technique can distinguish EBV DNA from patients with EBV-associated tumors (nasopharyngeal carcinoma, Hodgkin lymphoma) and viral DNA from patients without EBV-associated tumors, including immunocompromised patients and patients with EBV(−) Hodgkin lymphoma.
Quality of gout care in the emergency departments: a multicentre study
Authors: Towiwat Patapong , Phungoen Pariwat , Tantrawiwat Kitti , Laohakul Pavita , Aiewruengsurat Duangkamol , Thanadetsuntorn Chokchai , Ruchakorn Nopparat , Sangsawangchot Passagorn , Buttham Bodin 
Published: April 2020

Abstract
Background
To report on prevalence of gout flare in emergency departments and to report the quality of gout care in emergency departments and causes of admission at emergency departments.

Methods
A retrospective chart review of visits that had a primary diagnosis in gout by the International Classification of Diseases, the tenth revision, at emergency departments from 6 universities in Thailand over a 5 year period from 1 January 2012 to 31 December 2016.

Results
Six hundred thirty-two visits were included to the study. Prevalence of gout flare in emergency departments was 0.04. Only 29.3% of the visits had arthrocentesis. 628/632 (99.4%) and 519/585 (88.7%) of the visits were prescribed medications in emergency departments and had home medications, respectively. Although all visits that were prescribed colchicine in emergency departments received adequate doses of colchicine, it was also found that more than 2.4 mg/day of colchicine was prescribed (3/394, 0.8%) for home medications. In addition, 183/343 (53.4%) of the visits with normal renal function were prescribed non-steroidal anti-inflammatory drugs (NSAIDs). However, prescribed NSAIDs in abnormal renal function (42/343, 12.2%) was also found. The interruption of dosing, including increase, decrease, addition or discontinuance of urate lowing therapy in a gout flare period was 42/632 (6.6%). The most common cause of admission was acute gouty arthritis (31/47, 66.0%).

Conclusions
Quality of gout care in the emergency departments was not good. Inappropriate management of gout flare in emergency departments was demonstrated in our study, particularly with regard to investigations and pharmacological management. Gaps between clinicians and guidelines, the knowledge of clinicians, and overcrowding in emergency departments were hypothesized in the results.
Characteristics and outcome of spontaneous bacterial meningitis in patients with diabetes mellitus
Authors: Pomar Virginia , de Benito Natividad , Mauri Albert , Coll Pere , Gurguí Mercè , Domingo Pere 
Published: April 2020

Abstract
Background
Studies on bacterial meningitis in diabetics patients versus non-diabetics are scarce. In patients with diabetes, bacterial meningitis may have a different presentation, etiology and course. We analyzed and compared the characteristics and outcome of spontaneous BM in adult patients with and without diabetes mellitus (DM).

Methods
We performed a single-center, prospective observational cohort study, conducted between 1982 and 2017, in a tertiary university hospital in Barcelona (Spain). The primary outcome measure was in-hospital mortality.

Results
We evaluated 715 episodes of bacterial meningitis; 106 patients (15%) had diabetes mellitus. Patients with diabetes were older (median 67 [IQR 17] vs 49 [IQR 40] years, p <  0.001) and more often had a Charlson comorbidity score of ≥3 (40% vs 15%, p <  0.001). Neck stiffness (56% vs 75%, p <  0.001), headache (41% vs 78%) p <  0.001), nausea and/or vomiting (32% vs 56% p < 0.001), and rash (12% vs 26%, p = 0.007) were less frequent in diabetics, whereas altered mental status was more common. Streptococcus pneumoniae and Listeria meningitis were the most common etiologic agents (24 and 18%, respectively). Listeria was more frequent (18% vs. 10%, p = 0.033), whereas meningococcal meningitis was less frequent (10% vs 32%, p < 0.001). Overall mortality was higher in patients with diabetes (26% vs 16%, p = 0.025) concerning non-diabetics.

Conclusions
Patients with bacterial meningitis and diabetes mellitus are older, have more comorbidities, and higher mortality. S. pneumoniae and L. monocytogenes are the predominant pathogens, Listeria being more common, whereas Neisseria meningitidis is significantly less frequent than in non-diabetics.
Endocrine disorders after heart transplantation: national cohort study
Authors: Rakusa Matej , Vrtovec Bojan , Poglajen Gregor , Janez Andrej , Jensterle Mojca 
Published: April 2020

AbstractBackgroundEndocrine disorders in patients after heart transplantation (HT) remain understudied. We aimed to assess endocrine profiles and management of HT recipients in the early post- transplant period.MethodsWe conducted a retrospective cohort study on 123 consecutive HT recipients in the Advanced Heart Failure and Transplantation Programme between 2009 and 2018. All recipients had per-protocol endocrine follow-up within the first postoperative year. The median time to first post-transplant endocrine follow-up was 3 months (IQR 2–4). We assessed the incidence of vitamin D deficiency, bone mineral density, history of low energy fractures, hypogonadism in male recipients, posttransplant diabetes mellitus, and thyroid and parathyroid function.ResultsWe enrolled 22 women and 101 men of median age 57 years (IQR 50–63). Post-transplant diabetes mellitus developed in 14 patients (11.4%). 18 of 25 patients (14.6%) with preexisting type 2 diabetes mellitus required intensification of antidiabetic therapy. 38 male patients (40.4%) had hypogonadism. 5 patients (4.6%) were hypothyroid and 10 (9.3%) latent hyperthyroid. Secondary hyperparathyroidism was present in 19 (17.3%), 25-hydroxyvitamin D deficiency in 64 (54.7%) of patients. Osteoporosis was present in 26 (21.1%), osteopenia in 59 (48.0%) patients. 47 vertebral fractures, 3 hip and 1 humerus fractures occurred in 21 patients. Most of the patients had coincidence of two or three disorders, while less than 5% did not have any endocrine irregularities. All patients received calcium and vitamin D supplements. Forty-six patients (37.4%) were treated with zoledronic acid, 12 (9.8%) with oral bisphosphonates. Two patients were treated with teriparatide.ConclusionsThe prevalence of multiple endocrine disorders early after heart transplantation is high. Assessment and management of increased fracture risk and all other potentially affected endocrine axes should be considered as a standard of care in this early period.
What implies registered nurses’ leadership close to older adults in municipal home health care? A systematic review
Authors: Claesson Maria , Jonasson Lise-Lotte , Lindberg Elisabeth , Josefsson Karin 
Published: April 2020

Abstract
Background
Registered nurses are key figures in municipal home health care for older adults. Thus, registered nurses’ leadership is crucial to a successful and preventive care process as well as a supportive organization in order to achieve safe care. However, there is limited research on what registered nurses’ leadership implies close to older adults in municipal home health care. Thus, the aim is to compile and critically evaluate how international research results describe registered nurses’ leadership close to older adults in municipal home health care.

Methods
A systematic literature review was performed in accordance with a qualitative research study. The main search was conducted on 20 April 2018. The review was reported according to the PRISMA guidelines and is registered in the PROSPERO database (ID# CRD42019109206). Nine articles from PubMed and CINAHL meet the quality criteria. A synthesis of data was performed in four stages according to qualitative research synthesis.

Results
Ten themes describe what registered nurses’ leadership close to older adults in municipal home health care entails: trust and control; continuous learning; competence through knowledge and ability; nursing responsibility on an organizational level; application of skills; awareness of the individual’s needs and wholeness; mutual support; mutual relationships; collaborating on organizational and interpersonal levels; and exposure to challenges.

Conclusions
Registered nurses leading close to older adults in municipal home health care implies being multi-artists. Nursing education, including specialist education for registered nurses, should prepare individuals for their unique and complex leadership role as a multi-artist. Municipal employers require knowledge about what registered nurses’ leadership implies in order to create adequate conditions for their leadership objectives to achieve safe care. Further research is warranted to explore registered nurses’ leadership close to older adults in municipal home health care from different perspectives, such as older adults and next of kin.
Integrating evolutionarily novel horns within the deeply conserved insect head
Authors: Linz David M. , Moczek Armin P. 
Published: April 2020

Abstract
Background
How novel traits integrate within ancient trait complexes without compromising ancestral functions is a foundational challenge in evo-devo. The insect head represents an ancient body region patterned by a deeply conserved developmental genetic network, yet at the same time constitutes a hot spot for morphological innovation. However, the mechanisms that facilitate the repeated emergence, integration, and diversification of morphological novelties within this body region are virtually unknown. Using horned Onthophagus beetles, we investigated the mechanisms that instruct the development of the dorsal adult head and the formation and integration of head horns, one of the most elaborate classes of secondary sexual weapons in the animal kingdom.

Results
Using region-specific RNAseq and gene knockdowns, we (i) show that the head is compartmentalized along multiple axes, (ii) identify striking parallels between morphological and transcriptional complexity across regions, yet (iii) fail to identify a horn-forming gene module. Instead, (iv) our results support that sex-biased regulation of a shared transcriptional repertoire underpins the formation of horned and hornless heads. Furthermore, (v) we show that embryonic head patterning genes frequently maintain expression within the dorsal head well into late post-embryonic development, thereby possibly facilitating the repurposing of such genes within novel developmental contexts. Lastly, (vi) we identify novel functions for several genes including three embryonic head patterning genes in the integration of both posterior and anterior head horns.

Conclusions
Our results illuminate how the adult insect head is patterned and suggest mechanisms capable of integrating novel traits within ancient trait complexes in a sex- and species-specific manner. More generally, our work underscores how significant morphological innovation in developmental evolution need not require the recruitment of new genes, pathways, or gene networks but instead may be scaffolded by pre-existing developmental machinery.
Enabling and hindering factors of health surveillance assistants’ roles in the provision of contraceptive services in Mangochi, Malawi
Authors: Kok Maryse , Tolani Madalitso , Mtonga Wongani , Salamba Thom , Mwabungulu Twambilire , Munthali Arnold , Smet Eefje , Chinsakaso Benedict 
Published: April 2020

Abstract
Background
Contraceptive services are essential for promoting people’s health, and economic and social well-being. Despite increased contraceptive use over the past decades, unmet need is still high in Malawi. As a result of task shifting, health surveillance assistants (HSAs), Malawi’s paid community health worker cadre, provide an expanded range of contraceptive services, aimed at increasing access at community level. We conducted a qualitative study to explore enabling and hindering factors of HSAs’ roles in the provision of modern contraceptive services in Mangochi district, Malawi.

Methods
The study involved HSAs and their supervisors, a variety of community members, health workers and policy makers using 34 interviews and 12 focus group discussions. Data were recorded, transcribed, translated, coded and thematically analysed according to a framework that included community-, HSA- and health system-related factors.

Results
HSAs were found to be trusted providers of contraceptive services. At community level, gender norms, decision-making and beliefs about contraceptives were intertwined. They resulted in women using contraceptive services, including those offered by HSAs, in secret. There were misconceptions about contraceptives among both men and women, which were insufficiently addressed by HSAs. Residence and age of HSAs influenced their role in the provision of contraceptive services to (young) community members, whereas sex was not regarded as an enabling or hindering factor. While most community members reported to be satisfied with the quality of HSAs’ services, quality was compromised by a lack of contraceptive supplies and other resources, and limited supportive supervision and training.

Conclusions
HSAs in Mangochi are important contraceptive service providers. Their ability to ensure male involvement, increase access to services for youth and address misconceptions about contraceptives needs improvement. This requires a thorough understanding of socio-cultural norms and improved behavioural change communication competencies, which need to be incorporated in future training under Malawi’s Community Health Strategy.
A qualitative study on acceptability of the mistreatment of women during childbirth in Myanmar
Authors: Maung Thae Maung , Show Kyaw Lwin , Mon Nwe Oo , Tunçalp Özge , Aye Nyein Su , Soe Yin Yin , Bohren Meghan A. 
Published: April 2020

Abstract
Background
Improving the quality of maternal health care is critical to reduce mortality and improve women’s experiences. Mistreatment during childbirth in health facilities can be an important barrier for women when considering facility-based childbirth. Therefore, this study attempted to explore the acceptability of mistreatment during childbirth in Myanmar according to women and healthcare providers, and to understand how gender power relations influence mistreatment during childbirth.

Methods
A qualitative study was conducted in two townships in Bago Region in September 2015, among women of reproductive age (18–49 years), healthcare providers and facility administrators. Semi-structured discussion guides were used to explore community norms, and experiences and perceptions regarding mistreatment. Coding was conducted using athematic analysis approach and Atlas.ti. Results were interpreted using a gender analysis approach to explore how power dynamics, hierarchies, and gender inequalities influence how women are treated during childbirth.

Results
Women and providers were mostly unaccepting of different types of mistreatment. However, some provided justification for slapping and shouting at women as encouragement during labour. Different access to resources, such as financial resources, information about pregnancy and childbirth, and support from family members during labor might impact how women are treated. Furthermore, social norms around pregnancy and childbirth and relationships between healthcare providers and women shape women’s experiences. Both informal and formal rules govern different aspects of a woman’s childbirth care, such as when she is allowed to see her family, whether she is considered “obedient”, and what type of behaviors she is expected to have when interacting with providers.

Conclusions
This is the first use of gender analysis to explore how gender dynamics and power relations contribute to women’s experiences of mistreatment during childbirth. Both providers and women expected women to understand and “obey” the rules of the health facility and instructions from providers in order to have better experiences. In this way, deviation from following the rules and instructions puts the providers in a place where perpetrating acts of mistreatment were justifiable under certain conditions. Understanding how gender norms and power structures how women are treated during childbirth is critical to improve women’s experiences.
Role of data measurement characteristics in the accurate detection of Parkinson’s disease symptoms using wearable sensors
Authors: Shawen Nicholas , O’Brien Megan K. , Venkatesan Sanjeev , Lonini Luca , Simuni Tanya , Hamilton Jamie L. , Ghaffari Roozbeh , Rogers John A. , Jayaraman Arun 
Published: April 2020

Abstract
Background
Parkinson’s disease (PD) is a progressive neurological disease, with characteristic motor symptoms such as tremor and bradykinesia. There is a growing interest to continuously monitor these and other symptoms through body-worn sensor technology. However, limited battery life and memory capacity hinder the potential for continuous, long-term monitoring with these devices. There is little information available on the relative value of adding sensors, increasing sampling rate, or computing complex signal features, all of which may improve accuracy of symptom detection at the expense of computational resources. Here we build on a previous study to investigate the relationship between data measurement characteristics and accuracy when using wearable sensor data to classify tremor and bradykinesia in patients with PD.

Methods
Thirteen individuals with PD wore a flexible, skin-mounted sensor (collecting tri-axial accelerometer and gyroscope data) and a commercial smart watch (collecting tri-axial accelerometer data) on their predominantly affected hand. The participants performed a series of standardized motor tasks, during which a clinician scored the severity of tremor and bradykinesia in that limb. Machine learning models were trained on scored data to classify tremor and bradykinesia. Model performance was compared when using different types of sensors (accelerometer and/or gyroscope), different data sampling rates (up to 62.5 Hz), and different categories of pre-engineered features (up to 148 features). Performance was also compared between the flexible sensor and smart watch for each analysis.

Results
First, there was no effect of device type for classifying tremor symptoms (p > 0.34), but bradykinesia models incorporating gyroscope data performed slightly better (up to 0.05 AUROC) than other models (p = 0.01). Second, model performance decreased with sampling frequency (p < 0.001) for tremor, but not bradykinesia (p > 0.47). Finally, model performance for both symptoms was maintained after substantially reducing the feature set.

Conclusions
Our findings demonstrate the ability to simplify measurement characteristics from body-worn sensors while maintaining performance in PD symptom detection. Understanding the trade-off between model performance and data resolution is crucial to design efficient, accurate wearable sensing systems. This approach may improve the feasibility of long-term, continuous, and real-time monitoring of PD symptoms by reducing computational burden on wearable devices.
Intrapreneurship concepts for engineers: a systematic review of the literature on its theoretical foundations and agenda for future research
Authors: Alam Muhammad Zubair , Nasir Nadia , Rehman Ch. Abdul 
Published: April 2020

AbstractUnderstanding of intrapreneurship as a phenomenon is somewhat fragmented and inconsistent especially in the case of engineers or engineering firms. This paper seeks to assess the relevant intellectual territory of intrapreneurship or corporate entrepreneurship (CE) by taking a systematic review of relevant research to collect insights into research linking intrapreneurship with engineering firms. The purpose of the systematic review is to identify key concepts in intrapreneurial research with regard to engineers or engineering firms as deliberated by researchers in literature. This systematic literature review (SLR) found that the academic interest of researchers on intrapreneurship has increased over the last decade with a diverse focus. Based on the findings of the review, this study has suggested various areas for future research on the conceptual framework of intrapreneurship, relationship of intrapreneurship with corporate performance, and intrapreneurship for engineers.