bluuebunny/crossref_metadata_2025_split huggingface dataset:
Disease course of neurofibromatosis type 2: a 30-year follow-up study of 353 patients seen at a single institution
Authors: Forde Claire , King Andrew T , Rutherford Scott A , Hammerbeck-Ward Charlotte , Lloyd Simon K , Freeman Simon R , Pathmanaban Omar N , Stapleton Emma , Thomas Owen M , Laitt Roger D , Stivaros Stavros , Kilday John-Paul , Vassallo Grace , McBain Catherine , Kerrigan Simon , Smith Miriam J , McCabe Martin G , Harkness Elaine F , Evans D Gareth 
Published: December 2020

Abstract

Background
Limited data exist on the disease course of neurofibromatosis type 2 (NF2) to guide clinical trial design.

Methods
A prospective database of patients meeting NF2 diagnostic criteria, reviewed between 1990 and 2020, was evaluated. Follow-up to first vestibular schwannoma (VS) intervention and death was assessed by univariate analysis and stratified by age at onset, era referred, and inheritance type. Interventions for NF2-related tumors were assessed. Cox regression was performed to determine the relationship between individual factors from time of diagnosis to NF2-related death.

Results
Three hundred and fifty-three patients were evaluated. During 4643.1 follow-up years from diagnosis to censoring, 60 patients (17.0%) died. The annual mean number of patients undergoing VS surgery or radiotherapy declined, from 4.66 and 1.65, respectively, per 100 NF2 patients in 1990-1999 to 2.11 and 1.01 in 2010-2020, as the number receiving bevacizumab increased (2.51 per 100 NF2 patients in 2010-2020). Five patients stopped bevacizumab to remove growing meningioma or spinal schwannoma. 153/353 (43.3%) had at least one neurosurgical intervention/radiation treatment within 5 years of diagnosis. Patients asymptomatic at diagnosis had longer time to intervention and better survival compared to those presenting with symptoms. Those symptomatically presenting &lt;16 and &gt;40 years had poorer overall survival than those presenting at 26-39 years (P = .03 and P = .02, respectively) but those presenting between 16 and 39 had shorter time to VS intervention. Individuals with de novo constitutional variants had worse survival than those with de novo mosaic or inherited disease (P = .004).

Conclusion
Understanding disease course improves prognostication, allowing for better-informed decisions about care.
High frequency of disease progression in pediatric spinal cord low-grade glioma (LGG): management strategies and results from the German LGG study group
Authors: Perwein Thomas , Benesch Martin , Kandels Daniela , Pietsch Torsten , Schmidt René , Quehenberger Franz , Bison Brigitte , Warmuth-Metz Monika , Timmermann Beate , Krauss Jürgen , Thomale Ulrich-Wilhelm , Kortmann Rolf-Dieter , Driever Pablo Hernáiz , Gnekow Astrid Katharina 
Published: December 2020

Abstract

Background
Knowledge on management of pediatric spinal cord low-grade glioma (LGG) is scarce.

Methods
We analyzed clinical datasets of 128 pediatric patients with spinal LGG followed within the prospective multicenter trials HIT-LGG 1996 (n = 36), SIOP-LGG 2004 (n = 56), and the subsequent LGG-Interim registry (n = 36).

Results
Spinal LGG, predominantly pilocytic astrocytomas (76%), harbored KIAA1549-BRAF fusion in 14/35 patients (40%) and FGFR1-TACC1 fusion in 3/26 patients (12%), as well as BRAFV600E mutation in 2/66 patients (3%). 10-year overall survival (OS) and event-free survival (EFS) was 93% ± 2% and 38% ± 5%, respectively. Disseminated disease (n = 16) was associated with inferior OS and EFS, while age ≥11 years and total resection were favorable factors for EFS. We observed 117 patients following total (n = 24) or subtotal/partial resection (n = 74), biopsy (n = 16), or radiologic diagnosis only (n = 3). Eleven patients were treated first with chemotherapy (n = 9) or irradiation (n = 2). Up to 20.8 years after diagnosis/initial intervention, 73/128 patients experienced one (n = 43) or up to six (n = 30) radiological/clinical disease progressions. Tumor resections were repeated in 36 patients (range, 2-6) and 47 patients required nonsurgical treatment (chemotherapy, n = 20; radiotherapy, n = 10; multiple treatment lines, n = 17). Long-term disease control for a median of 6.5 (range, 0.02-20) years was achieved in 73/77 patients following one (n = 57) or repeated (n = 16) resections, and in 35/47 patients after nonsurgical treatment.

Conclusions
The majority of patients experienced disease progression, even after years. Multiple interventions were required for more than a third, yet multimodal treatment enabled long-term disease control. Molecular testing may reveal therapeutic targets.
The persistent presence of Chrysaora fulgida (Scyphozoa; Discomedusae) in the northern Benguela ecosystem is not reflected by constant recruitment
Authors: Skrypzeck Heidi , Gibbons Mark J 
Published: December 2020

Abstract
Unlike the situation in most temperate systems, medusae of Chrysaora (in this case, Chrysaora fulgida) are present year-round off Namibia, in a variety of size classes, implying the year-round release of ephyrae. This hypothesis was investigated by studying temporal changes in ephyrae and other gelatinous zooplankton in Walvis Bay over a 2-year period (January 2012 to December 2013), using biweekly plankton samples. All 12 of the recovered taxa were characteristically neritic and included meroplanktonic Hydrozoa and Scyphozoa as well as cydippid ctenophores and shallow water siphonophores. While ephyrae of C. fulgida were dominant overall and peaked in abundance during mid-spring, they were not present all year round, being replaced (in part) by medusae of Obelia in autumn and by the siphonophore Muggiaea atlantica in mid-summer and mid-winter. The structure of the assemblages was driven primarily by bottom water temperature and day length (explaining 27.2% of the variability in community structure). The recruitment of ephyrae of C. fulgida to the plankton off Walvis Bay is not continuous throughout the year, and this challenges our understanding of the population dynamics of this species in the region.
Emerging practices in onboarding programs for PAs
Authors: Anglin Lorraine , Sanchez Mara , Butterfield Rita , Rana Rachel , Everett Christine M. , Morgan Perri 
Published: December 2020

ABSTRACT

Objective:
This is the final article in a series that examines the role of onboarding programs for new physician assistants (PAs) and NPs. On-the-job learning is highly relevant for this workforce. Here we examine the strategies organizations use to impart information and skills in onboarding programs.

Methods:
In 2018, we interviewed 13 administrators of onboarding programs. Interviews were transcribed and analyzed for themes by a team of researchers, with feedback from interviewees.

Results:
Seven strategies were identified and are described in this article: Clinical mentoring, personal and professional mentoring, meeting with/shadowing other professionals, checking in by administrators, delivering didactic content, tailoring content or ramp-up, and assessing/ensuring competency.

Conclusions:
This article describes commonly used strategies in onboarding programs for PAs and NPs and can provide guidance to those designing their own onboarding programs. The programs we examined relied heavily on mentoring and other strategies appropriate for adult learners. Future work should evaluate the effectiveness of onboarding programs.
Are the new PA students helpful to emergency medicine physicians in Israel?
Authors: Berkowitz Oren , Maoz-Breuer Rina , Tal-Or Eran , Nissanholtz-Gannot Rachel 
Published: December 2020

ABSTRACT

Objective:
Physician assistants (PA) began training in Israeli EDs in 2016. Physician perspectives were measured to evaluate the clinical contributions of PA students.

Methods:
Investigators surveyed members of the Israeli Association of Emergency Medicine Physicians in 2017 to rate whether PA students were helpful in patient care and to explore perceptions about PA students.

Results:
Those working with a PA student felt they were helpful to very helpful in all of the clinical tasks measured. The majority (85%) of other physicians wanted to work with a PA student in the future. Ordering medications, administering IV fluid therapy, and suturing accounted for 60% of the tasks that physicians wanted to add to PA scope of practice.

Conclusions:
PA students were helpful in the ED and were meeting expectations for clinical contributions. Most physicians would like to work with PAs and they would like to see PAs increase their scope of practice.
Beyond roofies
Authors: Thompson Katherine M. 
Published: December 2020

ABSTRACT
Substance use in victims of sexual assault, whether voluntary or involuntary, changes the aftermath and recovery process significantly, affecting the way memories are processed and recalled, the chances of developing significant mental health complications, and the disclosure reactions that the survivor receives. Clinicians must understand these differences in order to provide the best possible care to survivors. This article provides an overview of these topics, detailing some of the nuances of interviewing, testing, and the physiology of memory formation and how that affects the outcomes of prosecution in these crimes.
The changing landscape of PAs and NPs in nephrology
Authors: Davis Jane , Zuber Kim 
Published: December 2020

ABSTRACT

Background:
Physician assistants (PAs) and NPs have expanded roles in nephrology as both the patient load and acuity of care needed for this population have increased.

Purpose:
To evaluate the workforce patterns of PAs and NPs working in nephrology over the past decade.

Methods:
Using the biannual survey from the National Kidney Foundation Council of Advanced Practitioners, data were collected and analyzed over the past decade.

Results:
Surveys of nephrology practitioners show the evolution of the dialysis-focused practitioner to one encompassing all aspects of nephrology: hospital, ICU, research, office, and all types of dialysis. Salaries and benefits have increased to compensate for the expansion of responsibilities.

Conclusions:
PAs and NPs in nephrology have the opportunity to use their skills and training in caring for this high-risk population.
33rd Annual APRN Legislative Update
Authors: Phillips Susanne J. 
Published: December 2020

Abstract:
In a year unlike any other in recent history, healthcare workers, including advanced practice registered nurses (APRNs), faced challenges and triumphs as the frontline in the battle against COVID-19. This 33rd Annual Legislative Update covers the scope of practice changes and legislative decisions that most impacted APRNs across the US in 2020.
High blood pressure induced by vitamin D deficiency is associated with renal overexpression and hyperphosphorylation of Na+-K+-2Cl- cotransporter type 2
Authors: Luchi Weverton M. , Crajoinas Renato O. , Martins Flavia L. , Castro Paulo de C. , Venturini Gabriela , Seguro Antonio C. , Girardi Adriana C.C. 
Published: December 2020

Objectives:
Clinical and epidemiological studies have suggested a correlation between vitamin D deficiency (VDD) and high blood pressure (BP). This study aimed to test the hypothesis that high BP induced by VDD is associated with altered expression and covalent modification of apical sodium transporters along the nephron. The contributions of the intrarenal renin–angiotensin system (RAS) and oxidative stress were also investigated.

Methods:
Male Wistar rats were fed a vitamin D-free (n = 26) or standard diet (n = 25) for 30 days. BP was recorded using noninvasive and invasive procedures. The expression levels of total and phosphorylated apical sodium transporters in rat renal cortex and medulla were evaluated by immunoblotting. Intrarenal RAS components were assessed by immunoblotting and ELISA. Renal oxidative stress was analyzed by measuring the concentrations of thiobarbituric acid reactive substances and reduced glutathione.

Results:
Higher BP levels in VDD rats than controls were accompanied by overexpression and hyperphosphorylation of renal cortical and medullary Na+-K+-2Cl- cotransporter type 2, enhanced levels of phosphorylated Na+/H+ exchanger type 3, and reduced expression levels of total and phosphorylated Na+/Cl- cotransporter. Changes in intrarenal RAS induced by VDD vs. controls included the marked elevation of medullary renin expression, higher expression of cortical angiotensinogen, higher urinary angiotensinogen excretion, and higher cortical and medullary angiotensin II content. VDD rats displayed higher thiobarbituric acid reactive substances/glutathione ratios in the renal cortex and medulla than controls.

Conclusion:
These results suggest that the molecular mechanisms underlying the effects of VDD on BP may include the upregulation of Na+-K+-2Cl- cotransporter type 2 and activation of intrarenal RAS and oxidative stress.
The Application of Exosomal MicroRNAs in the Treatment of Pancreatic Cancer and Its Research Progress
Authors: Li Xin , Jiang Wenkai , Gan Yu , Zhou Wence 
Published: December 2020

Abstract
Despite great progress in the treatment of pancreatic cancer under the efforts of researchers, the survival time of patients with pancreatic cancer is shorter than that of patients with other cancers. Thus, we have a great need for innovative therapeutic methods, including research and development of new drugs and innovation of administration methods. Exosomes are a type of extracellular vesicles wrapped by a lipid bilayer. Thanks to the low clearance ratio and strong specificity of exosomes in circulation, together with in-depth research on the surface protein of exosomes and a targeted modification method, there is a strong potential to apply exosomes in the transfer and even targeted delivery of chemotherapeutics, RNA, and natural products. Particularly, exosomes carrying microRNA show good application prospects in cancer therapy. This article is intended to summarize the progress of research relating to the treatment of pancreatic cancer via exosomal microRNAs.
Multicenter Retrospective Analysis of Chemotherapy for Advanced Pancreatic Acinar Cell Carcinoma
Authors: Takahashi Hideaki , Ikeda Masafumi , Shiba Satoshi , Imaoka Hiroshi , Todaka Akiko , Shioji Kazuhiko , Yane Kei , Kojima Yasushi , Kobayashi Satoshi , Asagi Akinori , Ozaka Masato , Takada Ryoji , Nagashio Yoshikuni , Horiguchi Shigeru , Kasuga Akiyoshi , Suzuki Eiichiro , Terashima Takeshi , Ueno Makoto , Morizane Chigusa , Furuse Junji 
Published: December 2020

Objectives
The aim of this multicenter retrospective study was to identify the optimal chemotherapeutic regimen for advanced pancreatic acinar cell carcinoma (PACC).

Methods
Fifty-eight patients with histopathologically confirmed advanced PACC who had received chemotherapy between 1996 and 2013 were enrolled. The clinical characteristics of the patients and the treatment efficacy data were collected from the medical records at 16 Japanese institutions, using standardized data collection instrument.

Results
The most commonly selected treatment regimens were gemcitabine-, fluoropyrimidine-, platinum-, and irinotecan-containing regimens. The overall response rate in the patients who received first-line chemotherapy were 7% and 38%, respectively, and the median overall survival was 13.2 months. When the data for all the treatment lines were aggregated, the response rates to gemcitabine-, fluoropyrimidine-, platinum-, and irinotecan-containing regimens were 7%, 18%, 40%, and 29%, respectively. The overall survival tended to be better in patients who had received a platinum-containing regimen (hazard ratio, 0.50; 95% confidence interval, 0.23–1.11; P = 0.08) or irinotecan-containing regimen (hazard ratio, 0.42; 95% confidence interval, 0.15–1.19; P = 0.09) at least once in the treatment course as compared with those who had not.

Conclusions
Our findings suggested that platinum- and irinotecan-containing regimens exhibited some potential efficacy in patients with advanced PACC.
Causes of Death After Neuroendocrine Tumors Diagnosis
Authors: Sonbol Mohamad Bassam , Saad Anas M. , Gonzalez-Velez Miguel , Starr Jason , Halfdanarson Thorvardur R. 
Published: December 2020

Objective
In this study, we aimed to determine the cause of death (COD) after the diagnosis of neuroendocrine tumors (NET).

Methods
We used the Surveillance, Epidemiology and End Results (SEER) Program to review patients diagnosed with NET during 2000 to 2016. Patients were followed until death, and different CODs were determined.

Results
Of 94,399 patients with NETs, 40.9% died during the study period. During the first year of diagnosis, most deaths were from NETs (73%), followed by other cancers (11.2%) and cardiac diseases (4.6%). After more than 10 years, NET deaths decreased to 24.3%, whereas other cancers and cardiac disease became more common. Neuroendocrine tumors were responsible for 42.8%, 63.4%, and 81.2% of deaths in grade I, grade II, and grade III, respectively. For grade I localized NET, other cancers (22.2%) were the most common COD followed by NET (19.7%), whereas in grade 2 localized NET, NET was COD in 31.1% of cases followed by other cancers (22.4%). In metastatic disease, NET was the most common COD regardless of grade.

Conclusions
For low-grade localized NET, deaths were mostly secondary to non-NET causes. In contrast, NET is responsible for most of deaths in metastatic NET regardless of grade.
Validation of a Clinical Prediction Rule to Predict Asymptomatic Chlamydia and Gonorrhea Infections Among Internet-Based Testers
Authors: Ablona Aidan , Falasinnu Titilola , Irvine Michael , Estcourt Claudia , Flowers Paul , Murti Michelle , Gómez-Ramírez Oralia , Fairley Christopher K. , Mishra Sharmistha , Burchell Ann , Grennan Troy , Gilbert Mark 
Published: December 2020

Background
Clinical prediction rules (CPRs) can be used in sexually transmitted infection (STI) testing environments to prioritize individuals at the highest risk of infection and optimize resource allocation. We previously derived a CPR to predict asymptomatic chlamydia and/or gonorrhea (CT/NG) infection among women and heterosexual men at in-person STI clinics based on 5 predictors. Population differences between clinic-based and Internet-based testers may limit the tool's application across settings. The primary objective of this study was to assess the validity, sensitivity, and overall performance of this CPR within an Internet-based testing environment (GetCheckedOnline.com).

Methods
We analyzed GetCheckedOnline online risk assessment and laboratory data from October 2015 to June 2019. We compared the STI clinic population used for CPR derivation (data previously published) and the GetCheckedOnline validation population using χ2 tests. Calibration and discrimination were assessed using the Hosmer-Lemeshow goodness-of-fit test and the area under the receiver operating curve, respectively. Sensitivity and the fraction of total screening tests offered were quantified for CPR-predicted risk scores.

Results
Asymptomatic CT/NG infection prevalence in the GetCheckedOnline population (n = 5478) was higher than in the STI clinic population (n = 10,437; 2.4% vs. 1.8%, P = 0.007). When applied to GetCheckedOnline, the CPR had reasonable calibration (Hosmer-Lemeshow, P = 0.90) and discrimination (area under the receiver operating characteristic, 0.64). By screening only individuals with total risk scores ≥4, we would detect 97% of infections and reduce screening by 14%.

Conclusions
The application of an existing CPR to detect asymptomatic CT/NG infection is valid within an Internet-based STI testing environment. Clinical prediction rules applied online can reduce unnecessary STI testing and optimize resource allocation within publicly funded health systems.
Efficacy, Safety, and Immunogenicity of Biosimilar Etanercept (Enerceptan) Versus Its Original Form in Combination With Methotrexate in Patients With Rheumatoid Arthritis
Authors: Strusberg Ingrid , Mysler Eduardo , Citera Gustavo , Siri Daniel , de los Ángeles Correa Maria , Lazaro Maria Alicia , Pardo Hidalgo Rodolfo , Spindler Alberto , Tate Patricio , Venarotti Horacio , Velasco Zamora Jorge , Klimovsky Ezequiel , Federico Andrea , Scheines Eduardo , Gonzalez Eliseo , Cordeiro Lucas , Lago Nestor 
Published: December 2020

Background
Enerceptan (EtaBS) has been developed as a proposed biosimilar of etanercept.

Methods
This randomized, multicenter, evaluator-blinded, noninferiority study conducted in Argentina included adults with active, moderate, and severe rheumatoid arthritis with inadequate response to methotrexate. Subjects were randomly assigned to 32 weeks treatment with EtaBS (n = 99) or etanercept (n = 51) at a weekly 50-mg dose administered subcutaneously. Patients were categorized according to prior use of biologic disease-modifying antirheumatic drugs and concomitant use of steroids. The primary efficacy endpoint was ACR20 response rate at week 32. Safety, immunogenicity, and steady-state concentration of both drugs were evaluated. The noninferiority margin for ACR20 was estimated at 12%.

Results
In the per-protocol population, 85 subjects (92.4%) treated with EtaBS and 44 subjects (93.6%) treated with etanercept achieved ACR20 (difference, −1.2%; 95% confidence interval, −10.1% to 7.6%). Frequent adverse drug reactions occurred in 34.3% and 38% of subjects treated with EtaBS and etanercept, respectively. The most common reaction was upper respiratory tract infection. Six and 3 serious adverse events occurred in 4 and 3 subjects treated with EtaBS and etanercept, respectively. Injection site reactions occurred in 67.7% and 66.0% of subjects treated with EtaBS and etanercept, respectively. Two subjects treated with EtaBS and 1 subject treated with etanercept developed antibodies by week 32.

Conclusions
Efficacy outcomes for EtaBS were noninferior to original etanercept in patients with moderate-to-severe rheumatoid arthritis with inadequate response to methotrexate. Safety and immunogenicity results were comparable between the two. This study is a major step toward improving access to biologics in Latin America.
Gordon Henry Dixon. 25 March 1930—24 July 2016
Authors: Oliva Rafael , Krawetz Stephen A. , Consortium GHD 
Published: December 2020

Gordon H. Dixon was a highly influential scientist who excelled in all the stages of his career and in each laboratory of every institution at which he was a member. Gordon began his graduate career at the University of Cambridge and completed his studies at the University of Toronto on the subject of transpeptidation reactions in biological systems. At an early stage of his career, he developed the technique of starch gel electrophoresis with Oliver Smithies and made important discoveries on the structure of human haptoglobins.
Subsequently, Gordon contributed to the determination of the structure and active sites and mechanisms of action of trypsin and chymotrypsin and made seminal discoveries related to understanding the structure of the protein hormone insulin. However, he is best known for his later studies on the regulation of protamine genes and chromatin transitions in spermatogenesis. He is often considered to be the father of the protamine molecular biology underlying this gene system and his research is continually cited to this day. Gordon contributed to the identification and sequencing of the protamine genes, the discovery that methionine was required for initiation of protamine synthesis, understanding the roles of histone hyperacetylation and protamine phosphorylation, and the generation of the highly compact nucleoprotamine structure present in sperm, primarily using trout as a model system. Gordon is fondly remembered as a brilliant and very generous scientist by all his mentees, representing all levels from undergraduates to PhD and postdoctoral fellows, who provided a scientifically stimulating atmosphere in which they could develop their careers. From a more personal perspective, he also had a fun side and was devoted to his family. Gordon was a person who, owing to his legacy of great science and his fundamental humanity, still lives in the memory of many people.