bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of a sterile compounding training and competency program at a large academic medical center
Authors: Penzien Carrie E , Tharp Jamie C , Mulzer Kristina , Rurka Craig , Abbas Chadi , Chaffee Bruce W 
Published: November 2020

Abstract

Purpose
This article is one of the 5 articles describing steps taken to enhance sterile compounding compliance at a large, multisite academic medical center. This article focuses on the development of a comprehensive personnel training and assessment program for sterile compounding.

Summary
Increased regulatory oversight and the release of new United States Pharmacopeia chapters motivated the reenvisioning of the medical center’s sterile compounding personnel training and assessment program. The main challenges facing any entity undertaking sterile compounding include identification of compounding staff, development of policies and procedures, and baseline and ongoing training including observational competency assessments and record keeping. These challenges are exacerbated by high work volumes and variation in compounding practices encountered within a large multisite institution. Our organization developed a team of specialized pharmacists and pharmacy technicians to implement and enforce changes promoting the safe production and use of compounded sterile products and meet rising regulatory requirements. This team worked within various operational areas to customize purchased policies and procedures and group compounding staff based on training needs. The team performs ongoing personnel monitoring and training of new compounders in a shared training space. Challenges encountered and future considerations for program enhancement are described.

Conclusion
Implementation of standards and enforcement of staff behaviors in a large academic medical center is perhaps best completed by a team of highly trained experts working in collaboration with supervisors and using a dedicated training and testing space, as evidenced by the success of the described program in overecoming past challenges.
‘Necessity is Neither Condemned nor Praised’: Social Workers’ Meanings of Guardianship for Disabled People
Authors: Holler R , Werner S 
Published: November 2020

Abstract
Throughout the years, disabled people, especially those with intellectual and mental disabilities, have frequently been appointed authorised guardians. Having been criticised for restricting individual freedom and autonomy and in line with the 2006 UN Convention on the Rights of Persons with Disabilities, a 2016 reform in Israel's Legal Capacity and Guardianship Law called for restricting the use of guardianship and preferring less restrictive alternatives, specifically supported decision making (SDM). The success of this reform rests largely on social workers. This study examined the meanings social worker attach to guardianship and SDM. In-depth semi-structured interviews were conducted with twenty-seven Israeli social workers. The findings showed that whilst they acknowledged the shortcomings of guardianship, they nevertheless perceived it to be vital. They provided three justifications for this view: guardianship as a safeguarding practice, guardianship as promoting individual well-being and guardianship in the service of third parties. These findings are discussed in terms of their meaning for guardianship as a risk-aversive practice designed to promote service users’ well-being and quality of life and in terms of the role played by third parties in bringing SDM into force. Recommended steps for moving the current reform in guardianship from paper to practice are highlighted.
Synergistic targeting of CHK1 and mTOR in MYC-driven tumors
Authors: Song Xiaoxue , Wang Liyuan , Wang Tianci , Hu Juncheng , Wang Jingchao , Tu Rongfu , Su Hexiu , Jiang Jue , Qing Guoliang , Liu Hudan 
Published: November 2020

Abstract
Deregulation of v-myc avian myelocytomatosis viral oncogene homolog (MYC) occurs in a broad range of human cancers and often predicts poor prognosis and resistance to therapy. However, directly targeting oncogenic MYC remains unsuccessful, and indirectly inhibiting MYC emerges as a promising approach. Checkpoint kinase 1 (CHK1) is a protein kinase that coordinates the G2/M cell cycle checkpoint and protects cancer cells from excessive replicative stress. Using c-MYC-mediated T-cell acute lymphoblastic leukemia (T-acute lymphoblastic leukemia) and N-MYC-driven neuroblastoma as model systems, we reveal that both c-MYC and N-MYC directly bind to the CHK1 locus and activate its transcription. CHIR-124, a selective CHK1 inhibitor, impairs cell viability and induces remarkable synergistic lethality with mTOR inhibitor rapamycin in MYC-overexpressing cells. Mechanistically, rapamycin inactivates carbamoyl-phosphate synthetase 2, aspartate transcarbamoylase, and dihydroorotase (CAD), the essential enzyme for the first three steps of de novo pyrimidine synthesis, and deteriorates CHIR-124-induced replicative stress. We further demonstrate that dual treatments impede T-acute lymphoblastic leukemia and neuroblastoma progression in vivo. These results suggest simultaneous targeting of CHK1 and mTOR as a novel and powerful co-treatment modality for MYC-mediated tumors.
Intrathoracic hand-sewn esophagogastric anastomosis in prone position during totally minimally invasive two-stage esophagectomy for esophageal cancer
Authors: Charalabopoulos Alexandros , Davakis Spyridon , Syllaios Athanasios , Lorenzi Bruno 
Published: November 2020

Summary
Utilization of totally minimally invasive esophagectomy for cancer is on the rise. Esophagogastric anastomosis is mechanically or robotically performed routinely; little report exists of hand-sewn esophagogastric anastomosis. This is the largest so far study with thoracoscopic hand-sewn esophagogastric anastomosis during fully minimally invasive two-stage esophagectomy for esophageal cancer in prone position. Consecutive two-stage totally minimally invasive esophagectomies for cancer were performed by one surgical team, from September 2016 to March 2019. All operations were technically identical in terms of patient positioning, surgical approach, extend of lymphadenectomy and type of anastomosis formed. Primary end points were anastomotic leak and anastomotic stricture rate, while secondary end points were 30-day and 90-day mortality rates. From the overall n = 80 patients, n = 67 were males, while n = 13 were females. Mean age was 64.6 years. Mean length of stay was n = 14 days. There were no conversions to open. Mean operating time was 420 minutes with no blood loss over 200 mL noted. Pulmonary and cardiac complication rate was 23.75% and 2.5%, respectively. Anastomotic leak rate was 2.5%. Anastomotic strictures were seen in 12.5% of cases. 30-day and 90-day mortality rate was 2.5% and 5%, respectively, with none accounted for ischemic conduit complications. Intrathoracic anastomosis in totally minimally invasive esophagectomy is challenging and accountable for most of the mortality associated with the procedure. In thoracoscopic two-stage esophagectomy, a mechanical anastomosis is usually preferred; this is believed to be due to the complexity of manual anastomosis associated with the thoracoscopic approach. We aim to present our series of completely hand-sewn intrathoracic anastomosis utilizing a totally minimally invasive approach with favorable outcomes. With this study, reproducibility of the anastomosis is shown that can potentially favor a change in the practice of esophageal surgeons worldwide.
30-year follow-up of an unoperated left atrial myxoma: a case report
Authors: Elsherif Zeinelabdien , Mahmood Naveed , Ahmed Amjad M 
Published: November 2020

Abstract

Background
Cardiac myxomas are the most common benign primary cardiac tumours. The natural history of left cardiac myxomas is thought to be of slowly growing tumours. Cardiac myxomas are a heterogeneous group with a variable growth rate. They present usually with stroke, valve obstruction, or non-specific symptoms. Surgical resection is the effective treatment.

Case summary
This case report describes a 56-year-old hypertensive and dyslipidaemic female, when she was admitted in January 1990, complaining of loss of appetite, aches, pains, and palpitations. Her workup included a transthoracic echocardiography and transoesophageal echocardiography, which showed a left atrial mass attached to the inter-atrial septum, highly suggestive of left atrial myxoma. She was referred for surgical removal of the left atrial mass. However, she was reluctant to undergo surgery as she felt better. The patient was followed-up for almost 30 years with the left atrial mass confirmed as left atrial myxoma by cardiac magnetic resonance imaging. The left atrial mass became smaller in size and more calcified.

Discussion
Cardiac myxomas are a group of heterogeneous tumours, thought to be slowly growing. The growth rate of cardiac myxomas prior to diagnosis is not well known, as the vast majority is treated with surgical resection immediately after diagnosis. Our case showed the natural progression of an unoperated smooth-surfaced left atrial myxoma followed-up for almost 30 years, which slowly became smaller and more calcified.
Case report: Managing profound circulatory collapse post-atrial fibrillation ablation: a methodical approach
Authors: Lim Ven Gee , Dhanjal Tarv , Panikker Sandeep , Osman Faizel 
Published: November 2020

Abstract

Background
Circulatory collapse during/post-pulmonary vein (PV) isolation by cryo-balloon ablation is a Cardiology emergency that has multiple potential causes and requires a methodical investigative approach. Some of the complications that can arise include cardiac tamponade, bleeding/vascular injury, anaphylaxis, Addisonian crisis, acute pulmonary embolism, acute PV stenosis, oesophageal injury, and vagal reaction.

Case summary
Here, we present a case of a 76-year-old lady who developed profound circulatory collapse during an elective pulmonary vein isolation by cryo-balloon ablation for symptomatic paroxysmal atrial fibrillation (AF). Cardiac tamponade, bleeding/vascular injury, and other less common causes were excluded. She only responded transiently to fluid resuscitation and developed intermittent bradyarrhythmias and hypotension which responded to isoprenaline. She was discharged home at Day 3 post-AF ablation after remaining well and continued to do so at follow-up.

Discussion
Circulatory collapse during/post-PV cryo-balloon ablation is a Cardiology emergency that has multiple potential causes. The ganglionate plexi form part of the cardiac intrinsic autonomic nervous system (ANS) and are located close to the left atrial–PV junctions. The presence of vagal response has been observed to be a marker of ANS modulation although its significance on the long-term outcome post-ablation has yet to be elucidated. The true cause of our patient’s profound circulatory collapse is uncertain but a vital learning point in this case is the systematic exclusion of common and potentially life-threatening complications following AF ablation. A persistent vagal reaction secondary to PV cryo-balloon ablation can usually be managed with supportive medical therapy as demonstrated in our case.
Influence of neprilysin inhibition on the efficacy and safety of empagliflozin in patients with chronic heart failure and a reduced ejection fraction: the EMPEROR-Reduced trial
Authors: Packer Milton , Anker Stefan D , Butler Javed , Filippatos Gerasimos , Ferreira Joao Pedro , Pocock Stuart J , Rocca Hans-Peter Brunner-La , Janssens Stefan , Tsutsui Hiroyuki , Zhang Jian , Brueckmann Martina , Jamal Waheed , Cotton Daniel , Iwata Tomoko , Schnee Janet , Zannad Faiez ,   for the EMPEROR-Reduced Trial Committees and Investigators
Published: November 2020

Abstract

Aims
We evaluated the influence of sacubitril/valsartan on the effects of sodium-glucose cotransporter 2 (SGLT2) inhibition with empagliflozin in patients with heart failure and a reduced ejection fraction.

Methods and results
The EMPEROR-Reduced trial randomized 3730 patients with heart failure and an ejection fraction ≤40% to placebo or empagliflozin (10 mg/day), in addition to recommended treatment for heart failure, for a median of 16 months. A total of 727 patients (19.5%) received sacubitril/valsartan at baseline. Analysis of the effect of neprilysin inhibition was 1 of 12 pre-specified subgroups. Patients receiving a neprilysin inhibitor were particularly well-treated, as evidenced by lower systolic pressures, heart rates, N-terminal prohormone B-type natriuretic peptide, and greater use of cardiac devices (all P &lt; 0.001) when compared with those not receiving sacubitril/valsartan. Nevertheless, when compared with placebo, empagliflozin reduced the risk of cardiovascular death or hospitalization for heart failure in patients receiving or not receiving sacubitril/valsartan [hazard ratio 0.64 (95% CI 0.45–0.89), P = 0.009 and hazard ratio 0.77 (95% CI 0.66–0.90), P = 0.0008, respectively, interaction P = 0.31]. Empagliflozin slowed the rate of decline in estimated glomerular filtration rate by 1.92 ± 0.80 mL/min/1.73 m2/year in patients taking a neprilysin inhibitor (P = 0.016) and by 1.71 ± 0.35 mL/min/1.73 m2/year in patients not taking a neprilysin inhibitor (P &lt; 0.0001), interaction P = 0.81. Combined inhibition of SGLT2 and neprilysin was well-tolerated.

Conclusion
The effects on empagliflozin to reduce the risk of heart failure and renal events are not diminished in intensively treated patients who are receiving sacubitril/valsartan. Combined treatment with both SGLT2 and neprilysin inhibitors can be expected to yield substantial additional benefits.
Galaxy CLIP-Explorer: a web server for CLIP-Seq data analysis
Authors: Heyl Florian , Maticzka Daniel , Uhl Michael , Backofen Rolf 
Published: November 2020

Abstract

Background
Post-transcriptional regulation via RNA-binding proteins plays a fundamental role in every organism, but the regulatory mechanisms lack important understanding. Nevertheless, they can be elucidated by cross-linking immunoprecipitation in combination with high-throughput sequencing (CLIP-Seq). CLIP-Seq answers questions about the functional role of an RNA-binding protein and its targets by determining binding sites on a nucleotide level and associated sequence and structural binding patterns. In recent years the amount of CLIP-Seq data skyrocketed, urging the need for an automatic data analysis that can deal with different experimental set-ups. However, noncanonical data, new protocols, and a huge variety of tools, especially for peak calling, made it difficult to define a standard.

Findings
CLIP-Explorer is a flexible and reproducible data analysis pipeline for iCLIP data that supports for the first time eCLIP, FLASH, and uvCLAP data. Individual steps like peak calling can be changed to adapt to different experimental settings. We validate CLIP-Explorer on eCLIP data, finding similar or nearly identical motifs for various proteins in comparison with other databases. In addition, we detect new sequence motifs for PTBP1 and U2AF2. Finally, we optimize the peak calling with 3 different peak callers on RBFOX2 data, discuss the difficulty of the peak-calling step, and give advice for different experimental set-ups.

Conclusion
CLIP-Explorer finally fills the demand for a flexible CLIP-Seq data analysis pipeline that is applicable to the up-to-date CLIP protocols. The article further shows the limitations of current peak-calling algorithms and the importance of a robust peak detection.
Use of dopamine agonists to target angiogenesis in women with endometriosis
Authors: Pellicer Nuria , Galliano Daniela , Herraiz Sonia , Bagger Yu Z , Arce Joan-Carles , Pellicer Antonio 
Published: November 2020

Abstract
Endometriosis requires medical management during a woman’s reproductive years. Most treatments aim to create a hypoestrogenic milieu, but for patients wishing to conceive, drugs that allow normal ovarian function are needed. Targeting angiogenesis, a hallmark of the disease, using dopamine agonists (DAs) is a promising strategy for endometriosis treatment. Herein, we review experimental and clinical data that investigate this concept. In experimental models of endometriosis, DAs (bromocriptine, cabergoline, quinagolide) downregulate proangiogenic and upregulate antiangiogenic pathways in inflammatory, endothelial and endometrial cells, blocking cellular proliferation and reducing lesion size. Impaired secretion of vascular endothelial growth factor (VEGF) and inactivation of its receptor type-2 are key events. VEGF inhibition also reduces nerve fiber density in lesions. In humans, quinagolide shows similar effects on lesions, and DAs reduce pain and endometrioma size. Moreover, a 20-fold downregulation of Serpin-1, the gene that encodes for plasminogen activator inhibitor 1 (PAI-1), has been observed after DAs treatment. Pentoxifylline, a PAI-1, increases pregnancy rates in women with endometriosis. Thus, the data support the use of DAs in the medical management of endometriosis to reduce lesion size and pain while maintaining ovulation. A combined approach of DAs and pentoxifylline is perhaps a smart way of targeting the disease from a completely different angle than current medical treatments.
Trends of Cancer-Related Suicide in the United States: 1999-2018
Authors: Han Xuesong , Hu Xin , Zhao Jingxuan , Ma Jiemin , Jemal Ahmedin , Yabroff K Robin 
Published: November 2020

Abstract
The suicide rate has steadily increased in the United States during the past 2 decades. Cancer patients have elevated suicide risk because of prevalent psychological distress, treatment side effects, and potentially uncontrolled pain. Efforts to promote psychosocial and palliative care may reduce this risk. Using the 1999-2018 Multiple Cause of Death database, we found a decreasing trend of cancer-related suicide during the past 2 decades with an average annual percentage change (AAPC) of age-adjusted suicide rates of -2.8% (95% confidence interval [CI] = -3.5% to -2.1%) in contrast to an increasing trend of overall suicide rate (AAPC = 1.7%, 95% CI = 1.5% to 1.8%). We also observed the largest declines in cancer-related suicide rates among high-risk populations including male, older age, and certain cancer types, suggesting an evolving role of psycho-oncology and palliative and hospice care during this period.
Malignant Peripheral Nerve Sheath Tumor in an Army Reservist With Neurofibromatosis Type 1
Authors: Kou Chung-Ting J , Rendo Matthew , Broadwater Devin R , Beeler Bradley 
Published: November 2020

ABSTRACT
Neurofibromatosis type 1 (NF1) is an autosomal dominant condition affecting 1 in 3,500 people resulting from an NF1 gene mutation that encodes the nonfunctional protein neurofibromin mutant. Neurofibromin is a negative regulator of RAS signaling involved in cell survival and proliferation. NF1 typically presents at birth or in early childhood with multiple light brown (café au lait) spots and axillary freckling. With age, patients may develop scattered neurofibromas as well as additional neurological and malignant abnormalities. Additionally, the nonfunctional protein neurofibromin mutant may be involved in the pathogenesis of peripheral malignant nerve sheath tumors, which is a rare and life-threatening complication of NF1. While a disqualifying condition for military duty, it may not initially be clinically apparent until complications develop. Here, we present a case of malignant peripheral sheath in an U.S. Army African American reservist with NF1 in whom cutaneous manifestations of NF1 such as café au lait spots and axillary freckling were not identified on the initial military entrance processing examination.
Full compressible 3D MHD simulation of solar wind
Authors: Matsumoto Takuma 
Published: November 2020

ABSTRACT
Identifying the heating mechanisms of the solar corona and the driving mechanisms of solar wind are key challenges in understanding solar physics. A full three-dimensional compressible magnetohydrodynamic (MHD) simulation was conducted to distinguish between the heating mechanisms in the fast solar wind above the open field region. Our simulation describes the evolution of the Alfvénic waves, which includes the compressible effects from the photosphere to the heliospheric distance s of 27 solar radii (R⊙). The hot corona and fast solar wind were reproduced simultaneously due to the dissipation of the Alfvén waves. The inclusion of the transition region and lower atmosphere enabled us to derive the solar mass-loss rate for the first time by performing a full three-dimensional compressible MHD simulation. The Alfvén turbulence was determined to be the dominant heating mechanism in the solar wind acceleration region (s &gt; 1.3 R⊙), as suggested by previous solar wind models. In addition, shock formation and phase mixing are important below the lower transition region (s &lt; 1.03 R⊙) as well.
Data-driven image restoration with option-driven learning for big and small astronomical image data sets
Authors: Jia Peng , Ning Runyu , Sun Ruiqi , Yang Xiaoshan , Cai Dongmei 
Published: November 2020

ABSTRACT
Image restoration methods are commonly used to improve the quality of astronomical images. In recent years, developments of deep neural networks and increments of the number of astronomical images have evoked a lot of data-driven image restoration methods. However, most of these methods belong to supervised learning algorithms, which require paired images either from real observations or simulated data as training set. For some applications, it is hard to get enough paired images from real observations and simulated images are quite different from real observed ones. In this paper, we propose a new data-driven image restoration method based on generative adversarial networks with option-driven learning. Our method uses several high-resolution images as references and applies different learning strategies when the number of reference images is different. For sky surveys with variable observation conditions, our method can obtain very stable image restoration results, regardless of the number of reference images.
Developing a unified pipeline for large-scale structure data analysis with angular power spectra – III. Implementing the multitracer technique to constrain neutrino masses
Authors: Tanidis Konstantinos , Camera Stefano 
Published: November 2020

ABSTRACT
In this paper, we apply the multitracer technique to harmonic-space (i.e. angular) power spectra with a likelihood-based approach. This goes beyond the usual Fisher matrix formalism hitherto implemented in forecasts with angular statistics, opening up a window for future developments and direct application to available data sets. We also release a fully operational modified version of the publicly available code CosmoSIS, where we consistently include all the add-ons presented in the previous papers of this series. The result is a modular cosmological parameter estimation suite for angular power spectra of galaxy number counts, allowing for single and multiple tracers, and including density fluctuations, redshift-space distortions, and weak-lensing magnification. We demonstrate the improvement on parameter constraints enabled by the use of multiple tracers on a multitracing analysis of luminous red galaxies and emission-line galaxies. We obtain an enhancement of $44{{\ \rm per\ cent}}$ on the 2σ upper bound on the sum of neutrino masses.