bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comprehensive metagenomic analysis of blastic plasmacytoid dendritic cell neoplasm
Authors: Nomburg Jason , Bullman Susan , Chung Sun Sook , Togami Katsuhiro , Walker Mark A. , Griffin Gabriel K. , Morgan Elizabeth A. , LeBoeuf Nicole R. , DeCaprio James A. , Meyerson Matthew , Lane Andrew A. 
Published: March 2020

AbstractBlastic plasmacytoid dendritic cell neoplasm (BPDCN) is a hematologic malignancy believed to originate from plasmacytoid dendritic cells (pDCs), the immune cells responsible for producing type 1 interferons during infection. Nearly all patients with BPDCN have prominent skin involvement, with cutaneous infiltration occupying the dermis and subcutis. One half of patients present with BPDCN cells only in the skin, with no evidence of disease elsewhere. Because normal pDCs are rare or absent in cutaneous sites, and they only traffic to the skin after activation by pathogen or inflammation, our aim was to determine if a microorganism is associated with BPDCN. We performed RNA sequencing in BPDCN skin and bone marrow, with cutaneous T-cell lymphoma (CTCL) and normal skin as controls. GATK-PathSeq was used to identify known microbial sequences. Bacterial reads in BPDCN skin were components of normal flora and did not distinguish BPDCN from controls. We then developed a new computational tool, virID (Viral Identification and Discovery; https://github.com/jnoms/virID), for identification of microbial-associated reads remaining unassigned after GATK-PathSeq. We found no evidence for a known or novel virus in BPDCN skin or bone marrow, despite confirming that virID could identify Merkel cell polyomavirus in Merkel cell carcinoma, human papillomavirus in head and neck squamous cell carcinoma, and Kaposi’s sarcoma herpesvirus in Kaposi’s sarcoma in a blinded fashion. Thus, at the level of sensitivity used here, we found no clear pathogen linked to BPDCN.
Treatment of MALT lymphoma of the conjunctiva with intralesional rituximab supplemented with autologous serum
Authors: Ferreri Andrés J. M. , Sassone Marianna , Miserocchi Elisabetta , Govi Silvia , Cecchetti Caterina , Corti Matteo E. , Mappa Silvia , Arcaini Luca , Zaja Francesco , Todeschini Giuseppe , Mannina Donato , Calimeri Teresa , Perrone Salvatore , Ponzoni Maurilio , Modorati Giulio 
Published: March 2020

Abstract
Patients with indolent conjunctival lymphomas exhibit good prognosis, with exceptional cases of dissemination, and are suitable candidates for intralesional therapies. We report the first prospective phase 2 trial using intralesional rituximab supplemented with autologous serum in adults with relapsed/refractory indolent CD20+ lymphoma of the conjunctiva (NCT01514344). Patients received 4 weekly intralesional injections of rituximab, followed by 6 monthly injections; 500 μL of autologous serum was added to rituximab in patients with lymphoma unresponsive to weekly doses. Safety, activity, and antitumor effect of autologous serum were investigated. Twenty patients with mucosa-associated lymphoid tissue (MALT)–type lymphoma were enrolled. Tolerability was excellent, with only 3 mild local reactions. After weekly injections, 11 patients achieved tumor regression, 8 had stable disease, and 1 experienced progressive disease; 9 patients received autologous serum, with response improvement in 4 cases (3 complete responses, 1 partial response). At the end of treatment, 12 patients achieved a complete remission, and 1 achieved a partial response, with an overall response rate of 65% (95% confidence interval, 45-85). At a median follow-up of 42 months (range, 10-78), 12 patients remain relapse free, with 5-year progression-free survival and time-to-next-treatment rates of 59% ± 11% and 69% ± 11%, respectively. Three patients with local relapse were retreated with intralesional rituximab and serum; 2 achieved a complete response that lasted 25+ and 38+ months. Thus, intralesional rituximab is a safe and active therapy in patients with relapsed conjunctival MALT lymphoma. The addition of autologous serum improves response in some cases. Retreatment of local relapses can result in a second durable remission.
Early detection of Ebola virus proteins in peripheral blood mononuclear cells from infected mice
Authors: Ward Michael D. , Kenny Tara , Bruggeman Ernie , Kane Christopher D. , Morrell Courtney L. , Kane Molly M. , Bixler Sandra , Grady Sarah L. , Quizon Rachel S. , Astatke Mekbib , Cazares Lisa H. 
Published: March 2020

Abstract
Background
Detection of viral ribo-nucleic acid (RNA) via real-time polymerase chain reaction (RT-PCR) is the gold standard for the detection of Ebola virus (EBOV) during acute infection. However, the earliest window for viral RNA detection in blood samples is 48–72 h post-onset of symptoms. Therefore, efforts to develop additional orthogonal assays using complementary immunological and serological technologies are still needed to provide simplified methodology for field diagnostics. Furthermore, unlike RT-PCR tests, immunoassays that target viral proteins and/or early host responses are less susceptible to sequence erosion due to viral genetic drift. Although virus is shed into the bloodstream from infected cells, the wide dynamic range of proteins in blood plasma makes this a difficult sample matrix for the detection of low-abundant viral proteins. We hypothesized that the isolation of peripheral blood mononuclear cells (PBMCs), which are the first cellular targets of the Ebola virus (EBOV), may provide an enriched source of viral proteins.

Methods
A mouse infection model that employs a mouse-adapted EBOV (MaEBOV) was chosen as a proof-of-principal experimental paradigm to determine if viral proteins present in PBMCs can help diagnose EBOV infection pre-symptomatically. We employed a liquid chromatography coupled with tandem mass spectrometry (LC–MS/MS) platform to provide both high sensitivity and specificity for the detection and relative quantitation of viral proteins in PBMCs collected during MaEBOV infection. Blood samples pooled from animals at the post-infection time-points were used to determine the viral load by RT-PCR and purify PBMCs.

Results
Using quantitative LC-MS/MS, we detected two EBOV proteins (vp40 and nucleoprotein) in samples collected on Day 2 post-infection, which was also the first day of detectable viremia via RT-PCR. These results were confirmed via western blot which was performed on identical PBMC lysates from each post-infection time point.

Conclusions
While mass spectrometry is not currently amenable to field diagnostics, these results suggest that viral protein enrichment in PBMCs in tandem with highly sensitive immunoassays platforms, could lead to the development of a rapid, high-throughput diagnostic platform for pre-symptomatic detection of EBOV infection.
Improving perception and confidence towards bystander cardiopulmonary resuscitation and public access automated external defibrillator program: how does training program help?
Authors: Liaw Siew Yee , Chew Keng Sheng , Zulkarnain Ahmad , Wong Shirly Siew Ling , Singmamae Nariman , Kaushal Dev Nath , Chan Hiang Chuan 
Published: March 2020

Abstract
Background
In conjunction with an automated external defibrillator (AED) placement program at various locations within a public university in Malaysia, a series of structured training programs were conducted. The objectives of this study is to (1) evaluate the effectiveness of a structured training program in improving the perception of the importance of AED and cardiopulmonary resuscitation (CPR), (2) evaluate the confidence of the employees in using an AED and performing bystander CPR, (3) identify the fears and concerns of these employees in using AED and performing CPR, and (4) determine the perception of these employees towards the strategy of the AEDs placed at various locations within the university.

Methods
In this single-center observational study, a validated questionnaire aimed to assess the university employees’ attitude and confidence in handling AED and performing CPR before (pre-test) and immediately after (post-test) the training program was conducted.

Results
A total of 184 participants participated in this study. Using the Wilcoxon signed-rank test, the training programs appeared to have improved the perception that “using AED is important for unresponsive victims” (z = 4.32, p < 0.001) and that “AED practice drills should be performed on a regular basis” (z = − 2.41, p = 0.02) as well as increased the confidence to perform CPR (z = − 8.56, p < 0.001), use AED (z = − 8.93, p < 0.001), identify victims with no signs of life (z = − 7.88, p < 0.001), and the willingness to perform CPR and AED without hesitancy (z = − 8.91, p < 0.001). Fears and concerns on performing CPR and using AED also appeared to have been significantly reduced, and the perception on placement strategies of these AEDs was generally positive.

Conclusion
Using the theory of planned behavior as the explanatory framework, training programs appear to be helpful in improving the perception and the confidence of the participants towards performing CPR and using AED through the promotion of positive attitude, positive societal expectation, and a positive sense of empowerment. But whether this positive effect will translate into actual CPR performance and AED application in a real cardiac arrest is yet to be seen.
ILK supports RhoA/ROCK-mediated contractility of human intestinal epithelial crypt cells by inducing the fibrillogenesis of endogenous soluble fibronectin during the spreading process
Authors: Gagné David , Benoit Yannick D. , Groulx Jean-François , Vachon Pierre H. , Beaulieu Jean-François 
Published: March 2020

Abstract
Background
Fibronectin (FN) assembly into an insoluble fibrillar matrix is a crucial step in many cell responses to extracellular matrix (ECM) properties, especially with regards to the integrin-related mechanosensitive signaling pathway. We have previously reported that the silencing of expression of integrin-linked kinase (ILK) in human intestinal epithelial crypt (HIEC) cells causes significant reductions in proliferation and spreading through concomitantly acquired impairment of soluble FN deposition. These defects in ILK-depleted cells are rescued by growth on exogenous FN. In the present study we investigated the contribution of ILK in the fibrillogenesis of FN and its relation to integrin-actin axis signaling and organization.

Results
We show that de novo fibrillogenesis of endogenous soluble FN is ILK-dependent. This function seemingly induces the assembly of an ECM that supports increased cytoskeletal tension and the development of a fully spread contractile cell phenotype. We observed that HIEC cell adhesion to exogenous FN or collagen-I (Col-I) is sufficient to restore fibrillogenesis of endogenous FN in ILK-depleted cells. We also found that optimal engagement of the Ras homolog gene family member A (RhoA) GTPase/Rho-associated kinase (ROCK-1, ROCK-2)/myosin light chain (MLC) pathway, actin ventral stress fiber formation, and integrin adhesion complex (IAC) maturation rely primarily upon the cell’s capacity to execute FN fibrillogenesis, independent of any significant ILK input. Lastly, we confirm the integrin α5β1 as the main integrin responsible for FN assembly, although in ILK-depleted cells αV-class integrins expression is needed to allow the rescue of FN fibrillogenesis on exogenous substrate.

Conclusion
Our study demonstrates that ILK specifically induces the initiation of FN fibrillogenesis during cell spreading, which promotes RhoA/ROCK-dependent cell contractility and maturation of the integrin-actin axis structures. However, the fibrillogenesis process and its downstream effect on RhoA signaling, cell contractility and spreading are ILK-independent in human intestinal epithelial crypt cells.
6q25.1 (TAB2) microdeletion is a risk factor for hypoplastic left heart: a case report that expands the phenotype
Authors: Cheng Andrew , Neufeld-Kaiser Whitney , Byers Peter H. , Liu Yajuan J. 
Published: March 2020

AbstractIntroductionHypoplastic left heart syndrome (HLHS) is a rare but devastating congenital heart defect (CHD) accounting for 25% of all infant deaths due to a CHD. The etiology of HLHS remains elusive, but there is increasing evidence to support a genetic cause for HLHS; in particular, this syndrome is associated with abnormalities in genes involved in cardiac development. Consistent with the involvement of heritable genes in structural heart abnormalities, family members of HLHS patients have a higher incidence of both left- and right-sided valve abnormalities, including bicuspid aortic valve (BAV).Case presentationWe previously described (Am J Med Genet A 173:1848–1857, 2017) a 4-generation family with a 6q25.1 microdeletion encompassingTAB2, a gene known to play an important role in outflow tract and cardiac valve formation during embryonic development. Affected adult family members have short stature, dysmorphic facial features, and multiple valve dysplasia, including BAV. This follow-up report includes previously unpublished details of the cardiac phenotype of affected family members. It also describes a baby recently born into this family who was diagnosed prenatally with short long bones, intrauterine growth restriction (IUGR), and HLHS. He was the second family member to have HLHS; the first died several decades ago. Postnatal genetic testing confirmed the baby had inherited the familialTAB2deletion.ConclusionsOur findings suggestTAB2haploinsufficiency is a risk factor for HLHS and expands the phenotypic spectrum of this microdeletion syndrome. Chromosomal single nucleotide polymorphism (SNP) microarray analysis and molecular testing for aTAB2loss of function variant should be considered for individuals with HLHS, particularly in those with additional non-cardiac findings such as IUGR, short stature, and/or dysmorphic facial features.
Patient motives for contacting out-of-hours care in Denmark: a cross-sectional study
Authors: Huibers Linda , Carlsen Anders H. , Moth Grete , Christensen Helle C. , Riddervold Ingunn S. , Christensen Morten B. 
Published: March 2020

Abstract
Background
Patients in need of acute health care do not always contact the most suitable health care service provider. Contacting out-of-hours primary care for an urgent problem may delay care, whereas contacting emergency medical services for a non-urgent problem could ultimately affect patient safety. More insight into patient motives for contacting a specific health care provider may help optimise patient flows. This study aims to explore patient motives for contacting out-of-hours primary care and the emergency medical services in Denmark.

Methods
We conducted a cross-sectional observational study by sending a questionnaire to patients contacting out-of-hours primary care and emergency medical services, both of which can be directly contacted by patients, in two of five Danish regions in 2015. As we aimed to focus on the first access point, the emergency department was not included. The questionnaire included items on patient characteristics, health problem and 26 pre-defined motives. Descriptive analyses of patient characteristics and motives were conducted, stratified by the two health care service providers. Factors associated with contacting each of the two service providers were explored in a modified Poisson regression analysis, and adjusted risk ratios were calculated.

Results
Three key motives for contacting the two service providers were identified: ‘unpleasant symptoms’, ‘perceived need for prompt action’ and ‘perceived most suitable health care provider’. Other important motives were ‘need arose outside office hours’ and ‘wanted to talk to a physician’ (out-of-hours primary care) and ‘expected need for ambulance’ and ‘worried’ (emergency medical services). Higher probability of contacting the emergency medical services versus out-of-hours primary care was seen for most motives relating to own assessment and expectations, previous experience and knowledge, and own needs and wishes. Lower probability was seen for most motives relating to perceived barriers and benefits.

Conclusions
Patient motives for contacting the two health care service providers were partly overlapping. The study contributes with new knowledge on the complex decision-making process of patients in need of acute health care. This knowledge could help optimise existing health care services, such as patient safety and the service level, without increasing health care costs.
Research methodology used in the 50 most cited articles in the field of pediatrics: types of studies that become citation classics
Authors: Jelicic Kadic Antonia , Kovacevic Tanja , Runjic Edita , Simicic Majce Ana , Markic Josko , Polic Branka , Mestrovic Julije , Puljak Livia 
Published: March 2020

AbstractBackgroundOne of the frequently used methods for assessing research trends and the impact of published scientific literature in a particular discipline is citation analysis. Journals may strive to improve their metrics by choosing manuscripts and study designs that are more likely to be cited. The aim of this study was to identify the 50 most-cited articles in the field of pediatrics, analyze their study design and other characteristics of those articles, and assess the prevalence of systematic reviews among them.MethodsIn December 2017, we searched Web of Science (WoS) for all articles published in the field of pediatrics. Two authors screened articles independently and in the further analysis included 50 articles with the highest number of citations. To avoid bias for scientific papers published earlier, the citation density was calculated. We also analyzed Journal Impact Factor (JIF) of journals where citation classics were published.ResultsThe citation density in top 50 cited articles in the field of pediatrics ranged from 33.16 to 432.8, with the average of 119.95. Most of the articles reported clinical science. Median 2016 JIF for journals that published them was 6.226 (range: 2.778 to 72.406). Half of the top 10 highly cited articles in pediatrics were published in a journal with JIF below 5. Most of the studies among the citation classics in pediatrics were cross-sectional studies (N = 22), followed by non-systematic narrative reviews (N = 10), randomized controlled trials (N = 5), cohort studies (N = 5), systematic reviews (N = 2), case-control studies (N = 2), case reports (N = 2), and there was one study protocol and one expert opinion.ConclusionFew randomized controlled trials and systematic reviews were among citation classics in the field of pediatrics. Articles that use observational research methodology, and are published in journals with lower impact factors, can become citation classics.
Non breathing-related sleep fragmentation and imaging markers in patients with atherosclerotic cerebral small vessel disease (CSVD): a cross-sectional case-control study
Authors: Wang Jihui , Chen Xiaodong , Liao Jinchi , Zhou Li , Han Hongying , Tao Jiong , Lu Zhengqi 
Published: March 2020

Abstract
Background
Sleep fragmentation was shown to be positively associated with cognitive impairment in patients with cerebral small vessel disease (CSVD); however, the underlying mechanisms are not well characterized. In this study, we sought to clarify this issue by investigating the relationship between non breathing-related sleep fragmentation and brain imaging markers in patients with CSVD.

Methods
Eighty-four CSVD patients and 24 age- and sex-matched healthy controls were prospectively recruited. All subjects underwent 3.0 T superconducting magnetic resonance imaging and overnight polysomnography. Polysomnography parameters including sleep onset latency (SOL), total sleep time (TST); sleep efficiency (SE), wake after sleep onset (WASO), percentage of each sleep stage (N1, N2, N3 and rapid eye movement [REM]), arousal index (ArI), periodic limb movement in sleep index (PLSMI), and periodic limb movement related arousal index (PLMAI) were compared between CSVD patients and healthy controls. The relationship between arousal index and CSVD markers was explored in the CSVD group.

Results
On polysomnography, CSVD patients showed significantly higher ArI, WASO, PLSMI, and PLMAI, and lower sleep efficiency and N− 3 ratio compared to healthy controls (p < 0.05). On ordinal logistic regression, higher ArI showed a positive association with the severity of periventricular white matter hyperintensity (odds ratio [OR] 1.121, 95% confidence interval [CI] 0.138–2.185) and perivascular space (OR 2.108, 95% CI 1.032–4.017) in CSVD patients, after adjusting for potential confounding variables.

Conclusions
These preliminary results indicate that non breathing-related sleep fragmentation is common and related to the pathological markers of CSVD patients. Future prospective research is required to determine the causal relationship between sleep parameters and CSVD pathology.
Investigatory pathway and principles of patient selection for epilepsy surgery candidates: a systematic review
Authors: Ghaffari-Rafi Arash , Leon-Rojas Jose 
Published: March 2020

AbstractBackgroundThe predominant treatment for epilepsy is pharmacotherapy, yet 20–40% do not respond to anti-epileptic drugs. After becoming pharmacoresistant, some patients are worked-up to determine candidacy for epilepsy surgery. Despite the 2009 American Epilepsy Society guidelines, there is no broadly accepted criteria for the investigatory pathway and principles of patient selection for epilepsy surgery candidates. The objective of this systematic review is to elucidate what diagnostic pathways clinicians globally utilize.MethodsUtilizing the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) and the Cochrane Handbook of Systemic Reviews of Interventions, we conducted a systematic review through MEDLINE, Embase, and CENTRAL.ResultsFrom 2092 screened articles, 14 met inclusion criteria for qualitative synthesis. Structural MRI was required in all investigatory pathways. All but two articles required neuropsychological assessment. Six required neuropsychiatric assessment. Two protocols mentioned assessing the patient’s support network. Three other protocols mentioned discussing expectations with patients. One also motioned conducing an occupational evaluation and making all surgery decisions in a multidisciplinary management conference. fMRI and the Wada test were required assessments in seven of the protocols. [18F]FDG-PET and SPECT were ancillary for all but three articles (where they were required). MEG and intracranial EEG were only mentioned as ancillary. Magnetic resonance (MR) spectroscopy was required at two institutes. With regards to the actual indication for selecting patients to begin the investigatory pathway, seven of the articles used a variation of the International League Against Epilepsy definition of refectory epilepsy, while one incorporated patient social history.ConclusionsDespite attempts to standardize patient selection and investigatory pathways, no two protocols were identical. Scalp video/EEG telemetry, structural MRI, and neuropsychological assessment were the only assessments utilized in nearly all protocols. Socioeconomic restrictions appear to play a role in determining which tests are utilized in the investigatory pathway—not just for developing countries. However, cost-effective assessments, such as assessing patient support network and providing realistic expectation of outcomes, were only utilized in few protocols. In addition, no advanced imaging technologies (i.e., qMRI, 3D-MMI) were utilized. Overall, even amongst expert examiners there is significant variation throughout epilepsy centers globally, in selecting candidates and working up patients.