bluuebunny/crossref_metadata_2025_split huggingface dataset:
Consensus-Based Guidelines for the Recognition, Diagnosis, and Management of Hemophagocytic Lymphohistiocytosis in Critically Ill Children and Adults
Authors: Hines Melissa R. , von Bahr Greenwood Tatiana , Beutel Gernot , Beutel Karin , Hays J. Allyson , Horne AnnaCarin , Janka Gritta , Jordan Michael B. , van Laar Jan A. M. , Lachmann Gunnar , Lehmberg Kai , Machowicz Rafal , Miettunen Päivi , La Rosée Paul , Shakoory Bita , Zinter Matt S. , Henter Jan-Inge 
Published: October 2021

OBJECTIVE:
Hemophagocytic lymphohistiocytosis is a hyperinflammatory syndrome that often requires critical care support and remains difficult to diagnose. These guidelines are meant to aid in the early recognition, diagnosis, supportive care, and treatment of patients with hemophagocytic lymphohistiocytosis in ICUs.

DATA SOURCES:
The literature searches were performed with PubMed (MEDLINE).

STUDY SELECTION:
Keywords and medical subject headings terms for literature search included “macrophage activation syndrome,” hemophagocytic lymphohistiocytosis,” and “hemophagocytic syndrome.”

DATA EXTRACTION:
The Histiocyte Society developed these consensus recommendations on the basis of published reports and expert opinions with level of evidence provided for each recommendation. They were endorsed by the Society of Critical Care Medicine.

DATA SYNTHESIS:
Testing for hemophagocytic lymphohistiocytosis should be initiated promptly in all patients admitted to ICUs with an unexplained or disproportionate inflammatory response, especially those with rapid clinical deterioration. Meeting five or more of eight hemophagocytic lymphohistiocytosis 2004 diagnostic criteria serves as a valuable diagnostic tool for hemophagocytic lymphohistiocytosis. Early aggressive critical care interventions are often required to manage the multisystem organ failure associated with hemophagocytic lymphohistiocytosis. Thorough investigation of the underlying triggers of hemophagocytic lymphohistiocytosis, including infections, malignancies, and autoimmune/autoinflammatory diseases, is essential. Early steroid treatment is indicated for patients with familial hemophagocytic lymphohistiocytosis and is often valuable in patients with acquired hemophagocytic lymphohistiocytosis (i.e., secondary hemophagocytic lymphohistiocytosis) without previous therapy, including macrophage activation syndrome (hemophagocytic lymphohistiocytosis secondary to autoimmune/autoinflammatory disease) without persistent or relapsing disease. Steroid treatment should not be delayed, particularly if organ dysfunction is present. In patients with macrophage activation syndrome, whose disease does not sufficiently respond, interleukin-1 inhibition and/or cyclosporine A is recommended. In familial hemophagocytic lymphohistiocytosis and severe, persistent, or relapsing secondary macrophage activation syndrome, the addition of prompt individualized, age-adjusted etoposide treatment is recommended.

CONCLUSIONS:
Further studies are needed to determine optimal treatment for patients with hemophagocytic lymphohistiocytosis in ICUs, including the use of novel and adjunct therapies.
Epilepsy in children with perinatal arterial ischemic stroke
Authors: Kühne Fabienne , Jungbluth Alexander , Schneider Joanna , Bührer Christoph , Prager Christine , Kaindl Angela M. 
Published: October 2021

ABSTRACTPurposePerinatal ischemic stroke (PIS) is a frequent cause for perinatal brain structure defects resulting in epilepsy, cerebral palsy and disability. Since the severity of symptoms is variable, the aim of this study was to evaluate the outcome of children with PIS and seizures/epilepsy to aid parental counseling and therapy decisions.MaterialWe studied retrospectively patients with arterial PIS and structural epilepsy or seizures in the newborn treated at a single center in 2000-2019. Specifically, signs and symptoms of cerebral palsy (CP), developmental and motor delay, epilepsy and thrombophilia were assessed.ResultsFrom the identified 69 individuals with arterial PIS, we only included the 50 patients (64% male) who had structural epilepsy at the time of investigation or previously in their medical history.The mean age of the included patients was 7.1 years (range 0.08-22) at last consultation. Infarct localisation was predominantly unilateral (86%), left sided (58%) and affecting the middle cerebral artery (94%). Genetic thrombophilia was identified in 52% of the patients examined with genetic testing. More than half of the individuals had CP (52%), and 38.5% had a cognitive outcome below average. First seizures occurred in the neonatal period in 58% of patients and developed into drug-refractory epilepsy in 24.1%. Children with late-onset of epilepsy were twice as likely to develop drug-refractory epilepsy (52.4%).DiscussionOur study shows that patients with PIS and seizures as common sequela often also develop CP. Children with later onset of epilepsy have a worse outcome. Patients with seizure onset in the neonatal period and reccuring seizures have a good response to treatment. Therefore, early diagnosis, follow-up examination and adequate therapy are important. Most children need intensive physiotherapy and speech therapy; however, participation in life is usually age-appropriate.
Evaluation of liver function tests and C-reactive protein in COVID-19 (SARS Cov-2) positive patients diagnosed by Real-time PCR
Authors: Khurshid Fatima , Iqbal Sajjad , Mumtaz Madiha 
Published: October 2021

ABSTRACTBACKGROUND AND AIMSThe SARS-CoV-2 pandemic, has caused an unconventional social and economic impact globally. To date, there was limited data regarding the effect of COVID-19 infection on the trend of RT-PCR Ct value, risk factors for disease, effect on liver enzymes, etc. This study aimed to assess the frequency of COVID-19 infection in different age groups and genders. Association of cycle threshold (Ct) values with disease severity and to describe the effect of COVID-19 infection on LFT, Deritis ratio, and CRP. That can be used as indicators for COVID-19 infection diagnosis, the guidance for treatment decisions, and prognosis in infected individuals.METHODSThis was a cross-sectional study conducted in the Molecular Biology and Chemical Pathology sections of the Pathology Department, Shalamar Teaching Hospital Lahore from November 2020 to March 2021.ResultsMales 51% were more likely to be infected by SARS-CoV-2. Most of the infected individuals 36.5% were in the age group 20-40. Age and underlying comorbidities are important factors that play a significant role in COVID-19 severity. The uppermost number of the patients had symptoms of fever 78.3%, cough 50.4% and myalgias 50.1% RT-PCR low Ct value could be an important indicator related with the disease severity and mortality risk p value < 0.001 and 0.003 respectively. Bilirubin indirect, ALT, AST, and CRP were significantly associated with disease severity. Deritis ratio and CRP was found to be significantly associated with the risk of mortality.CONCLUSIONSReal-Time PCR results along with Ct values for SARS-CoV-2 may have benefit for clinicians in patient management decisions. Several risk factors e.g., age and comorbidities for developing severe disease and mortality risk have been identified. These biochemical laboratory parameters ALT, AST, Deritis ratio and CRP can be used as predictive biomarkers for progression towards severe disease and risk of mortality.
Telemedicine and molecular Sars-CoV-2 early detection to face the COVID-19 pandemic
Authors: Cherem José , Pylro Victor Satler , Poles Katia , Carvalho Richardson Costa , Carvalho Ewerton , dos Santos Juliana Anacleto , Alvarenga Ingrid Marciano , Rocha Denise Alvarenga , Teixeira Karla Silva , de Castro Joseane Camilla , Torquete Mariana Almeida , de Almeida Ferreira Sidney , de Paiva Barçante Joziana Muniz 
Published: October 2021

AbstractThe COVID-19 pandemic brought a series of challenges to the academic community. Social distancing measures imposed the interruption of face-to-face activities besides the implementation of remote work and online classes. For safe and gradual return, the monitoring of individuals, quick detection of infection, contact tracing, and isolation of those infected became essential. In this sense, we developed strategies to face the pandemic at the Federal University of Lavras (UFLA) - Brazil. A Telemedicine Program (TeleCovid) and the assemblage of a laboratory for SARS-CoV-2 molecular diagnosis (LabCovid) were essential measures for monitoring, preventing, and controlling outbreaks at the university. TeleCovid works with a team of students who guide and answer questions regarding COVID-19 and, when necessary, make the referral for online consultation with medical professionals. In the suspicion of SARS-CoV-2 infection, the doctor refers the patient for testing at LabCovid. LabCovid performs the sample collection using nasal swabs, followed by processing samples by the RT-qPCR method. We have placed all positive patients in isolation and tested their contacts. This approach meant that positive cases were identified early, thus avoiding outbreaks in different environments in face-to-face activities.
Characteristics associated with COVID-19 vaccination status among staff and faculty of a large, diverse University in Los Angeles
Authors: Nicolo Michele , Kawaguchi Eric , Ghanem-Uzqueda Angie , Kim Andre E. , Soto Daniel , Deva Sohini , Shanker Kush , Rogers Christopher , Lee Ryan , Casagrande Yolee , Gilliland Frank , Orman Sarah Van , Klausner Jeffery , Kovacs Andrea , Conti David , Hu Howard , Unger Jennifer B. 
Published: October 2021

AbstractObjectiveThis study examined characteristics associated with being unvaccinated among a sample of university staff and faculty prior to university campus reopening for in-person learning in spring-summer 2021.MethodsStaff and faculty responded to an email invitation to complete an online survey. Survey questions included demographic data (race/ethnicity, age, sex), COVID-19 knowledge and behaviors, employment specific data including division and subdivision (healthcare vs. non-healthcare related division); and self-reported vaccination status. A multivariable logistic regression analysis was performed to determine significant characteristics associated with the likelihood of being unvaccinated for COVID-19.ResultsParticipants identifying as Asian and Asian American, Hispanic/Latinx or Multicultural/Other had greater odds of being unvaccinated compared to Non-Hispanic White participants. Other characteristics associated with greater likelihood of being unvaccinated included working as university staff member (vs. faculty), older age, decrease in income, inability to work remotely and not traveling outside of Los Angeles area. Political affiliation as an Independent or as something else were more likely to be unvaccinated compared to participants identifying as Democrat.ConclusionsFindings suggest several factors associated with racial and social disparities may delay the uptake of COVID-19 vaccination. This study highlights the need for targeted educational interventions to promote vaccination among university staff and faculty.
Electrocardiogram Analysis of Post-Stroke Elderly People Using One-dimensional Convolutional Neural Network Model with Gradient-weighted Class Activation Mapping
Authors: Ho Eric S. , Ding Zhaoyi 
Published: October 2021

AbstractBackground and purposesStroke is the second leading cause of death globally after ischemic heart disease, also a risk factor of cardioembolic stroke. Thus, we postulate that heartbeats encapsulate vital signals related to stroke. With the rapid advancement of deep neural networks (DNNs), it emerges as a powerful tool to decipher intriguing heartbeat patterns associated with post-stroke patients. In this study, we propose the use of a one-dimensional convolutional network (1D-CNN) architecture to build a binary classifier that distinguishes electrocardiogram s (ECGs) between the post-stroke and the stroke-free.MethodsWe have built two 1D-CNNs that were used to identify distinct patterns from an openly accessible ECG dataset collected from elderly post-stroke patients. In addition to prediction accuracy, which is the primary focus of existing ECG deep neural network methods, we have utilized Gradient-weighted Class Activation Mapping (GRAD-CAM) to ease model interpretation by uncovering ECG patterns captured by our model.ResultsOur stroke model has achieved ∼90% accuracy and 0.95 area under the Receiver Operating Characteristic curve. Findings suggest that the core PQRST complex alone is important but not sufficient to differentiate the post-stroke and the stroke-free.ConclusionsWe have developed an accurate stroke model using the latest DNN method. Importantly, our work has illustrated an approach to enhance model interpretation, overcoming the black-box issue facing DNN, fostering higher user confidence and adoption of DNN in medicine.
Equivalence of saliva RT-qPCR testing to nasal-throat/nasopharyngeal swab testing in the general practitioner’s setting to detect SARS-CoV-2
Authors: Jonckheere Ilse , Faes Liesbeth , Overmeire Yarah , De Vleeschauwer An , Vanden Daele Laura , Van Bruaene Nathalie , Vandecandelaere Ilse , Merlaen Britt , van Cann Joannes , Vandesompele Jo 
Published: October 2021

AbstractStudy designSaliva has been proposed as valid alternative for nasopharyngeal swab for RT-qPCR detection of SARS-CoV-2. The sensitivity is generally equivalent, and it comes with much less discomfort for the patient. While there is an overall good performance in the literature for adults, there is much less information on the use of saliva in children or in the general practitioner’s setting.MethodsWe tested a novel commercially available saliva collection kit with a virus inactivating and RNA stabilizing buffer (InActiv Blue®) in matched saliva and swab samples from 245 individuals, including 216 children, collected by general practitioners.ResultsBlind RT-qPCR testing of the saliva samples confirmed all 23 positives identified by swab testing (100% concordance), irrespective of age, presence of symptoms, or high-risk status. One child’s saliva sample was found low positive while negative on the nasopharyngeal swab, resulting in an overall relative sensitivity of RT-qPCR saliva testing of 104.3%.ConclusionSaliva collected in InActiv Blue® can be a valid alternative for SARS-CoV-2 RT-qPCR testing in the general practitioner’s setting, including children.
Humoral and cellular immune responses upon SARS-CoV-2 vaccines in patients with anti-CD20 therapies: A systematic review and meta-analysis of 1342 patients
Authors: Schietzel Simeon , Anderegg Manuel A. , Limacher Andreas , Born Alexander , Horn Michael P. , Maurer Britta , Hirzel Cédric , Sidler Daniel , Moor Matthias B. 
Published: October 2021

AbstractBackgroundImmune responses upon SARS-CoV-2 vaccination in patients receiving anti-CD20 therapies are impaired but vary considerably. We conducted a systematic review and meta-analysis of the literature on SARS-CoV-2 vaccine induced humoral and cell-mediated immune response in patients previously treated with anti-CD20 antibodies.MethodsWe searched PubMed, EMBASE, Medrxiv and SSRN using variations of search terms “anti-CD20”, “vaccine” and “COVID” and included original studies up to August 21st,2021. We excluded studies with missing data on humoral or cell-mediated immune response, unspecified methodology of response testing, unspecified timeframes between vaccination and blood sampling or low number of participants (≤ 3). We excluded individual patients with prior SARS-CoV-2 infection or incomplete vaccine courses. Primary endpoints were humoral and cell-mediated immune response rates. Pre-specified subgroups were time of vaccination after anti-CD20 therapy (< vs > 6 months), time point of response testing after vaccination (< vs > 4 weeks) and disease entity (autoimmune vs cancer vs renal transplant). We used random-effects models of proportions.FindingsNinety studies were assessed. Inclusion criteria were met by 23 studies comprising 1342 patients. Overall rate of humoral response was 0.41 (95% CI 0.35 – 0.47). Overall rate of cell-mediated immune responses was 0.71 (95% CI 0.47 – 0.90). Longer time interval since last anti-CD20 therapy was associated with higher humoral response rates > 6 months 0.63 (95% CI 0.53 – 0.72) vs < 6 months 0.2 (95% CI 0.03 – 0.43); p = 0.001. Compared to patients with haematological malignancies or autoimmune diseases, anti-CD20 treated kidney transplant recipients showed the lowest vaccination response rates.InterpretationPatients on anti-CD20 therapies can develop humoral and cell-mediated immune responses after SARS-CoV-2 vaccination, but subgroups such as kidney transplant recipients or those with very recent B-cell depleting therapy are at high risk for non-seroconversion and should be individually assessed for personalized SARS-CoV-2 vaccination strategies. Potential limitations are small patient numbers, heterogeneous diseases and assays used.FundingThis study was funded by Bern University Hospital.
Physician-confirmed and administrative definitions of stroke in UK Biobank reflect the same underlying genetic trait
Authors: Rannikmäe Kristiina , Rawlik Konrad , Ferguson Amy C , Avramidis Nikos , Jiang Muchen , Pirastu Nicola , Shen Xia , Davidson Emma , Woodfield Rebecca , Malik Rainer , Dichgans Martin , Tenesa Albert , Sudlow Cathie 
Published: October 2021

AbstractBackgroundStroke in UK Biobank (UKB) is ascertained via linkages to coded administrative datasets and self-report. We studied the accuracy of these codes using genetic validation.MethodsWe compiled stroke-specific and broad cerebrovascular disease (CVD) code lists (Read V2/V3, ICD-9/-10) for medical settings (hospital, death record, primary care) and self-report. Among 408,210 UKB participants we identified all with a relevant code, creating 12 stroke definitions based on the code type and source. We performed genome-wide association studies (GWASs) for each definition, comparing summary results against the largest published stroke GWAS (MEGASTROKE), assessing genetic correlations, and replicating 32 stroke-associated loci.ResultsStroke case numbers identified varied widely from 3,976 (primary care stroke-specific codes) to 19,449 (all codes, all sources). All 12 UKB stroke definitions were significantly correlated with the MEGASTROKE summary GWAS results (rg 0.81-1) and each other (rg 0.4-1). However, Bonferroni-corrected confidence intervals were wide, suggesting limited precision of some results. Six previously reported stroke-associated loci were replicated using ≥1 UKB stroke definitions.ConclusionsStroke case numbers in UKB depend on the code source and type used, with a 5-fold difference in the maximum case-sample size. All stroke definitions are significantly genetically correlated with the largest stroke GWAS to date.
Keeping students connected and engaged in a wet-lab research experience during a time of social distancing via mobile devices and video conferencing software
Authors: Shamoon-Pour Michel , Light Caitlin J. , Fegley Megan 
Published: October 2021

AbstractTwo major COVID-19 pandemic challenges presented for in-person instruction included adhering to social distancing guidelines and accommodating remote learners who were temporarily isolated or permanently participating from afar. At Binghamton University, our First-year Research Immersion (FRI) program was challenged with providing students with a wet lab course-based undergraduate research experience (CURE), an intense hands-on experience that emphasized student teamwork, lab protocol development, iteration, troubleshooting and other elements of the process of science that could not be replicated in a fully remote environment. We developed an innovative technology approach to maximize all students’ connection to the lab research experience utilizing dedicated mobile devices (iPod Touch) and video conferencing software (Zoom) to synchronously connect remote learners to in-person learners, peer mentors and instructors in our FRI research labs. In this way, despite limited lab capacities and fluctuating remote learning populations, we were able to connect remote learners to their peers and mentors in real-time and give them responsibilities that allowed them to be engaged and feel like meaningful participants in the research process. Although our students reported a preference for in-person labs, they noted this hybrid model was better than other traditionally employed remote-learning lab options. We believe lessons learned here can be applied to improve access to research in all situations and allow us to be prepared for other catastrophic disruptions to the educational system.
Classifying Literature Extracted Events for Automated Model Extension
Authors: Hansen Casey , Kisslinger Julia , Krishna Neal , Holtzapple Emilee , Ahmed Yasmine , Miskov-Zivanov Natasa 
Published: October 2021

1SUMMARYIn this study, we investigate the integration of three previously developed tools: FLUTE, VIOLIN, and CLARINET. We show how using these tools together adds additional capabilities in extending models from relevant research literature. We illustrate how we plan to address current modeling pitfalls with these tools (such as machine reading errors and literature volume), and how we plan to use these tools as the foundation for an automated model extension framework. Documentation and links to our tools can be found at:
violin-tool.readthedocs.ioclarinet-docs.readthedocs.ioflute.readthedocs.io
Organoid co-culture model of the cycling human endometrium in a fully-defined synthetic extracellular matrix reveals epithelial-stromal crosstalk
Authors: Gnecco Juan S. , Brown Alexander , Buttrey Kira , Ives Clara , Goods Brittany A. , Baugh Lauren , Hernandez-Gordillo Victor , Loring Megan , Isaacson Keith , Griffith Linda G. 
Published: October 2021

SummaryThe human endometrium undergoes recurring cycles of growth, differentiation, and breakdown in response to sex hormones. Dysregulation of epithelial-stromal communication during hormone cycles is linked to myriad gynecological disorders for which treatments remain inadequate. Here, we describe a completely defined, synthetic extracellular matrix that enables co-culture of human endometrial epithelial and stromal cells in a manner that captures healthy and disease states across a simulated menstrual cycle. We parsed cycle-dependent endometrial integrin expression and matrix composition to define candidate cell-matrix interaction cues for inclusion in a polyethylene glycol (PEG)-based hydrogel crosslinked with matrix metalloproteinase-labile peptides. We semi-empirically screened a parameter space of biophysical and molecular features representative of the endometrium to define compositions suitable for hormone-driven expansion and differentiation of epithelial organoids, stromal cells, and co-cultures of the two cell types. Each cell type exhibited characteristic morphological and molecular responses to hormone changes when co-encapsulated in hydrogels tuned to a stiffness regime similar to the native tissue and functionalized with a collagen-derived adhesion peptide (GFOGER) and a fibronectin-derived peptide (PHSRN-K-RGD). Analysis of cell-cell crosstalk during IL-1β-induced inflammation revealed dysregulation of epithelial proliferation mediated by stromal cells. Altogether, we demonstrate the development of a fully synthetic matrix to sustain the dynamic changes of the endometrial microenvironment and support its applications to understand menstrual health and endometriotic diseases.Abstract Figure