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Inter-individual variation in gene regulatory elements is hypothesized to play a causative role in adverse drug reactions and reduced drug activity. However, relatively little is known about the location and function of drug-dependent elements. To uncover drug-associated elements in a genome-wide manner, we performed RNA-seq and ChIP-seq using antibodies against the pregnane X receptor (PXR) and three active regulatory marks (p300, H3K4me1, H3K27ac) on primary human hepatocytes treated with rifampin or vehicle control. Rifampin and PXR were chosen since they are part of the CYP3A4 pathway, which is known to account for the metabolism of more than 50% of all prescribed drugs. We selected 227 proximal promoters for genes with rifampin-dependent expression or nearby PXR/p300 occupancy sites and assayed their ability to induce luciferase in rifampin-treated HepG2 cells, finding only 10 (4.4%) that exhibited drug-dependent activity. As this result suggested a role for distal enhancer modules, we searched more broadly to identify 1,297 genomic regions bearing a conditional PXR occupancy as well as all three active regulatory marks. These regions are enriched near genes that function in the metabolism of xenobiotics, specifically members of the cytochrome P450 family. We performed enhancer assays in rifampin-treated HepG2 cells for 42 of these sequences as well as 7 sequences that overlap linkage-disequilibrium blocks defined by lead SNPs from pharmacogenomic GWAS studies, revealing 15/42 and 4/7 to be functional enhancers, respectively. A common African haplotype in one of these enhancers in the GSTA locus was found to exhibit potential rifampin hypersensitivity. Combined, our results further suggest that enhancers are the predominant targets of rifampin-induced PXR activation, provide a genome-wide catalog of PXR targets and serve as a model for the identification of drug-responsive regulatory elements.

Epilepsy surgery is highly successful in achieving seizure freedom in carefully selected children with drug-resistant focal epilepsy. Advances in technology have aided presurgical evaluation and increased the number of possible candidates. Many of the tests employed are resource intense, and in specific cases they may be unhelpful or have adverse effects. Some standardization of the evaluation process is thus considered timely. Given the lack of class 1 or 2 evidence defining the relative utility of each test in specific clinicopathologic cohorts, a set of expert recommendations was attempted using consensus among members of the Pediatric Epilepsy Surgery Task Force of the International League Against Epilepsy (ILAE) Commissions of Pediatrics and Diagnostics These recommendations aim to limit fringe over or underutilization of use while retaining substantial flexibility in the use of various tests, in keeping with most standard practices at established pediatric epilepsy centers. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.

Historically, safety in the gastrointestinal (GI) endoscopy unit has focused on infection control, particularly around the reprocessing of endoscopes. Two highly publicized outbreaks where the transmission of infectious agents were related to GI endoscopy have highlighted the need to address potential gaps along the endoscopy care continuum that could impact patient safety.

Class IV dental diode lasers have been introduced as a nonsurgical therapy for periodontal pockets in veterinary and human dentistry. This retrospective case series evaluates the use of Class IV dental diode laser therapy for abnormal periodontal pockets in a specialty veterinary dental practice. A hypothesis that the Class IV diode dental laser is a useful adjuvant modality in canine periodontal pocket therapy in the reduction of clinical pocket depth was made. This article discusses and demonstrates diode laser use in periodontal pocket therapy in a specialty veterinary dental practice and reviews the current literature. Inclusion in this study was limited to client-owned dogs with noted periodontal pocketing on any tooth type between 3 and 6 mm, which were treated with closed root planing (RP/C) and laser therapy who returned in 6 to 7 months for recheck of the pockets from the years 2017 to 2020. Twelve patients met the inclusion criteria. A total of 128 periodontal pockets were included in the study. Each periodontal pocket was a case receiving therapy. The mean periodontal pocket depth before the treatment is measured as 3.35 mm. The mean pocket depth of the periodontal pockets following treatment was 0.59 mm. The mean improvement in periodontal pocket depths after diode laser therapy when considering patient and tooth number using linear mixed-effects modeling was 2.63 mm (95% confidence interval [CI]: 1.81-3.46, P <.0001). No statistically significant results were observed for pocket type, as P values were greater than.05. [ABSTRACT FROM AUTHOR]

Abstract The number of available therapies for rare diseases remains low, as fewer than 6% of rare diseases have an approved treatment option. The International Rare Diseases Research Consortium (IRDiRC) set up the multi-stakeholder Data Mining and Repurposing (DMR) Task Force to examine the potential of applying biomedical data mining strategies to identify new opportunities to use existing pharmaceutical compounds in new ways and to accelerate the pace of drug development for rare disease patients. In reviewing past successes of data mining for drug repurposing, and planning for future biomedical research capacity, the DMR Task Force identified four strategic infrastructure investment areas to focus on in order to accelerate rare disease research productivity and drug development: (1) improving the capture and sharing of self-reported patient data, (2) better integration of existing research data, (3) increasing experimental testing capacity, and (4) sharing of rare disease research and development expertise. Additionally, the DMR Task Force also recommended a number of strategies to increase data mining and repurposing opportunities for rare diseases research as well as the development of individualized and precision medicine strategies.

Abstract Background Over the last decade, multiple large randomized controlled trials have studied alternative transfusion strategies in critically ill patients, demonstrating the safety of restrictive transfusion strategies. Due to the lack of international guidelines specific for the intensive care unit (ICU), we hypothesized that a large heterogeneity in transfusion practice in this patient population exists. The aims of this study were to describe the current transfusion practices and identify the knowledge gaps. Methods An online, anonymous, worldwide survey among ICU physicians was performed evaluating red blood cell, platelet and plasma transfusion practices. Furthermore, the presence of a hospital- or ICU-specific transfusion guideline was asked. Only completed surveys were analysed. Results Nine hundred forty-seven respondents filled in the survey of which 725 could be analysed. Hospital transfusion protocol available in their ICU was reported by 53% of the respondents. Only 29% of respondents used an ICU-specific transfusion guideline. The reported haemoglobin (Hb) threshold for the general ICU population was 7 g/dL (7–7). The highest reported variation in transfusion threshold was in patients on extracorporeal membrane oxygenation or with brain injury (8 g/dL (7.0–9.0)). Platelets were transfused at a median count of 20 × 109 cells/L IQR (10–25) in asymptomatic patients, but at a higher count prior to invasive procedures (p 3, 43% and 57% of the respondents would consider plasma transfusion without any upcoming procedures or prior to a planned invasive procedure, respectively. Finally, doctors with base specialty in anaesthesiology transfused critically ill patients more liberally compared to internal medicine physicians. Conclusion Red blood cell transfusion practice for the general ICU population is restrictive, while for different subpopulations, higher Hb thresholds are applied. Furthermore, practice in plasma and platelet transfusion is heterogeneous, and local transfusion guidelines are lacking in the majority of the ICUs.

Abstract Background Rare Disease research has seen tremendous advancements over the last decades, with the development of new technologies, various global collaborative efforts and improved data sharing. To maximize the impact of and to further build on these developments, there is a need for model consent clauses for rare diseases research, in order to improve data interoperability, to meet the informational needs of participants, and to ensure proper ethical and legal use of data sources and participants’ overall protection. Methods A global Task Force was set up to develop model consent clauses specific to rare diseases research, that are comprehensive, harmonized, readily accessible, and internationally applicable, facilitating the recruitment and consent of rare disease research participants around the world. Existing consent forms and notices of consent were analyzed and classified under different consent themes, which were used as background to develop the model consent clauses. Results The IRDiRC-GA4GH MCC Task Force met in September 2018, to discuss and design model consent clauses. Based on analyzed consent forms, they listed generic core elements and designed the following rare disease research specific core elements; Rare Disease Research Introductory Clause, Familial Participation, Audio/Visual Imaging, Collecting, storing, sharing of rare disease data, Recontact for matching, Data Linkage, Return of Results to Family Members, Incapacity/Death, and Benefits. Conclusion The model consent clauses presented in this article have been drafted to highlight consent elements that bear in mind the trends in rare disease research, while providing a tool to help foster harmonization and collaborative efforts.

Abstract The NA60 experiment has studied low-mass muon pair production in proton–nucleus collisions with a system of Be, Cu, In, W, Pb and U targets, using a 400 GeV proton beam at the CERN SPS. The transverse momentum spectra of the $$\rho /\omega $$ ρ/ω and $$\phi $$ ϕ mesons are measured in the full $$p_{\mathrm {T}}$$ pT range accessible, from $$p_{\mathrm {T}}= 0$$ pT=0 up to $$2 \, {\hbox {GeV/c}}$$ 2GeV/c . The nuclear dependence of the production cross sections of the $$\eta $$ η , $$\omega $$ ω and $$\phi $$ ϕ mesons has been found to be consistent with the power law $$\sigma _{\mathrm {pA}} \propto {\mathrm {A}}^\alpha $$ σpA∝Aα , with the $$\alpha $$ α parameter increasing as a function of $$p_{\mathrm {T}}$$ pT for all the particles, and an approximate hierarchy $$\alpha _\eta \approx \alpha _\phi > \alpha _\omega $$ αη≈αϕ>αω . The cross section ratios $$\sigma _\eta /\sigma _\omega $$ ση/σω , $$\sigma _\rho /\sigma _\omega $$ σρ/σω and $$\sigma _\phi /\sigma _\omega $$ σϕ/σω have been studied as a function of the size A of the production target, and an increase of the $$\eta $$ η and $$\phi $$ ϕ yields relative to the $$\omega $$ ω is observed from p–Be to p–U collisions.

Abstract Tumor immunology has changed the landscape of cancer treatment. Yet, not all patients benefit as cancer immune responsiveness (CIR) remains a limitation in a considerable proportion of cases. The multifactorial determinants of CIR include the genetic makeup of the patient, the genomic instability central to cancer development, the evolutionary emergence of cancer phenotypes under the influence of immune editing, and external modifiers such as demographics, environment, treatment potency, co-morbidities and cancer-independent alterations including immune homeostasis and polymorphisms in the major and minor histocompatibility molecules, cytokines, and chemokines. Based on the premise that cancer is fundamentally a disorder of the genes arising within a cell biologic process, whose deviations from normality determine the rules of engagement with the host’s response, the Society for Immunotherapy of Cancer (SITC) convened a task force of experts from various disciplines including, immunology, oncology, biophysics, structural biology, molecular and cellular biology, genetics, and bioinformatics to address the complexity of CIR from a holistic view. The task force was launched by a workshop held in San Francisco on May 14–15, 2018 aimed at two preeminent goals: 1) to identify the fundamental questions related to CIR and 2) to create an interactive community of experts that could guide scientific and research priorities by forming a logical progression supported by multiple perspectives to uncover mechanisms of CIR. This workshop was a first step toward a second meeting where the focus would be to address the actionability of some of the questions identified by working groups. In this event, five working groups aimed at defining a path to test hypotheses according to their relevance to human cancer and identifying experimental models closest to human biology, which include: 1) Germline-Genetic, 2) Somatic-Genetic and 3) Genomic-Transcriptional contributions to CIR, 4) Determinant(s) of Immunogenic Cell Death that modulate CIR, and 5) Experimental Models that best represent CIR and its conversion to an immune responsive state. This manuscript summarizes the contributions from each group and should be considered as a first milestone in the path toward a more contemporary understanding of CIR. We appreciate that this effort is far from comprehensive and that other relevant aspects related to CIR such as the microbiome, the individual’s recombined T cell and B cell receptors, and the metabolic status of cancer and immune cells were not fully included. These and other important factors will be included in future activities of the taskforce. The taskforce will focus on prioritization and specific actionable approach to answer the identified questions and implementing the collaborations in the follow-up workshop, which will be held in Houston on September 4–5, 2019.

Summary: The role of the transforming growth factor (TGF)-β pathway in myocardial fibrosis is well recognized. However, the precise role of this signaling axis in cardiomyocyte (CM) biology is not defined. In TGF-β signaling, SMAD4 acts as the central intracellular mediator. To investigate the role of TGF-β signaling in CM biology, the authors deleted SMAD4 in adult mouse CMs. We demonstrate that CM-SMAD4–dependent TGF-β signaling is critical for maintaining cardiac function, sarcomere kinetics, ion-channel gene expression, and cardiomyocyte survival. Thus, our findings raise a significant concern regarding the therapeutic approaches that rely on systemic inhibition of the TGF-β pathway for the management of myocardial fibrosis. Key Words: cardiomyocyte, cardiomyopathy, fibrosis, heart failure, SMAD4, TGF-β

Introduction: The incidence of anal cancer in United States has increased over of the last few decades impacting immunosuppressed populations like solid organ transplant recipients, in particular. The aim of this study was to evaluate the prevalence of anal dysplasia among solid organ transplant patients. We also attempted to identify factors that predispose solid organ transplant recipients to developing anal dysplasia. Methods and materials: Patients presenting to transplant office for routine care were recruited to participate in the study. All anal cytology specimens were collected using standard anal pap technique. The results were assessed using Bethesda classification. Information on perceived risk factors for development of anal dysplasia among our subjects was obtained. Results: Among 80 patients approached, 47 agreed to participate in the study. Of all the samples 19.1% had an inadequate amount of specimen to perform any analysis. Dysplastic cells were found in 10.5% of the specimens available for analysis. We were not able to identify any risk factors including age, gender distribution, smoking, and duration of immunosuppression that were statistically significant different between patients with anal dysplasia versus those without anal dysplasia. Conclusions: The rate of anal dysplasia detectable on cytology is high enough to warrant anal dysplasia screening in transplant recipients, which can then be followed up with high-resolution anoscopy with biopsy. Defining a cohort of patients among solid organ transplant recipients who are at an increased risk for the development of anal dysplasia mandating screening continues to be a challenge. Resumo: Introdução: A incidência de câncer anal nos Estados Unidos aumentou nas últimas décadas, afetando populações imunossuprimidas, especialmente receptores de órgãos sólidos. O objetivo deste estudo foi avaliar a prevalência de displasia anal entre pacientes que receberam transplante de órgãos sólidos. Os autores buscaram identificar fatores que predispõem os receptores de transplante de órgãos sólidos a desenvolverem displasia anal. Métodos e materiais: Pacientes que se apresentaram ao consultório de transplante para acompanhamento de rotina foram recrutados para participar do estudo. Todos os espécimes de citologia foram coletados usando a técnica padrão de Papanicolau anal. Os resultados foram avaliados usando a classificação de Bethesda. Foram coletados dados sobre os fatores de risco percebidos para o desenvolvimento de displasia anal entre os participantes. Resultados: Dos 80 pacientes abordados, 47 concordaram em participar do estudo. Do total de amostras, 19,1% tinham uma quantidade inadequada para realizar qualquer análise. Células displásicas foram encontradas em 10,5% dos espécimes disponíveis para análise. Não foi possível identificar quaisquer fatores de risco, incluindo idade, distribuição de gênero, tabagismo e duração da imunossupressão, que foram estatisticamente diferentes entre pacientes com displasia anal e aqueles sem displasia anal. Conclusões: A taxa de displasia anal detectável na citologia é alta o suficiente para justificar a triagem em receptores de transplante, que pode então ser acompanhada com anuscopia de alta resolução com biópsia. A definição de triagem para uma coorte de pacientes entre os receptores de transplantes de órgãos sólidos que apresentam risco aumentado para o desenvolvimento displasia anal continua a ser um desafio. Keywords: Anal cancer, Anal dysplasia screening, Immunosupressed, Transplant recipients, Palavras-chave: Câncer anal, Triagem de displasia anal, Imunossuprimido, Receptores de transplantes

Cerebral cavernous malformations (CCMs) are well-defined, mostly singular lesions present in 0.4-0.9% of the population. Epileptic seizures are the most frequent symptom in patients with CCMs and have a great impact on social function and quality of life. However, patients with CCM-related epilepsy (CRE) who undergo surgical resection achieve postoperative seizure freedom in only about 75% of cases. This is frequently because insufficient efforts are made to adequately define and resect the epileptogenic zone. The Surgical Task Force of the Commission on Therapeutics of the International League Against Epilepsy (ILAE) and invited experts reviewed the pertinent literature on CRE. Definitions of definitive and probable CRE are suggested, and recommendations regarding the diagnostic evaluation and etiology-specific management of patients with CRE are made. Prospective trials are needed to determine when and how surgery should be done and to define the relations of the hemosiderin rim to the epileptogenic zone.

Chad E Eckert,1 Jason L Harris,1 Jordan B Wong,1 Suzanne Thompson,2 Edmund S Kassis,3 Masahiro Tsuboi,4 Harald C Ott,5 Seth Force6 1Ethicon Inc., Research and Development, Cincinnati, OH 45242, USA; 2Ethicon Inc., Preclinical Center of Excellence, Cincinnati, OH 45242, USA; 3Ethicon Inc., Medical Affairs, Cincinnati, OH 45242, USA; 4Division of Thoracic Surgery and Oncology, National Cancer Center Hospital East, Kashiwanoha, Kashiwa, Chiba 277-8577, Japan; 5Department of Surgery, Division of Thoracic Surgery, Massachusetts General Hospital, Boston, MA 02114, USA; 6Department of Surgery, Division of Cardiothoracic Surgery, Emory University Hospital, Atlanta, GA 30322, USA Purpose: Thoracic air leaks are a common complication following pulmonary resections. Limitations in clinical studies and preclinical models have hindered efforts to understand the pathophysiology of air leaks. With an emphasis on staple-line specific air leaks, we hypothesize that ventilation modality – intraoperative positive pressure vs postoperative negative pressure – and stapler design may play a role in air leaks. Methods: Using a novel physiologic lung model, air leaks associated with graduated and uniform staple designs were evaluated under positive and negative pressure ventilation, simulating perioperative breathing in porcine lungs. Air leak incidence, air leak volume, and air leak rate were captured along with ventilation pressure and tidal volume. Results: In all cases, negative pressure ventilation was associated with a higher occurrence of leaks when compared to positive pressure ventilation. Lungs leaked more air and at a faster rate under negative pressure ventilation compared to positive pressure ventilation. Graduated staple designs were associated with higher occurrence of leaks as well as larger leak rates when compared to uniform staples. Tissue thickness was not associated with differences in air leaks when tested with appropriate staple heights. Conclusion: Using a novel lung model to investigate the pathophysiology of air leaks, we have identified breathing modality and staple design as two important variables that may impact air leaks. This work will help guide device design and drive future studies in human tissue, and it may help inform clinical practice to ultimately improve patient outcomes. Keywords: prolonged air leak, lung physiology, preclinical model, surgical stapler, ventilation mechanics

Abstract Background Discovered and described 40 years ago, non‐specific lipid transfer proteins (nsLTP) are present in many plant species and play an important role protecting plants from stressors such as heat or drought. In the last 20 years, sensitization to nsLTP and consequent reactions to plant foods has become an increasing concern. Aim The aim of this paper is to review the evidence for the structure and function of nsLTP allergens, and cross‐reactivity, sensitization, and epidemiology of nsLTP allergy. Materials and Methods A Task Force, supported by the European Academy of Allergy & Clinical Immunology (EAACI), reviewed current evidence and provide a signpost for future research. The search terms for this paper were “Non‐specific Lipid Transfer Proteins”, “LTP syndrome”, “Pru p 3”, “plant food allergy”, “pollen‐food syndrome”. Results Most nsLTP allergens have a highly conserved structure stabilised by 4‐disulphide bridges. Studies on the peach nsLTP, Pru p 3, demonstrate that nsLTPs are very cross‐reactive, with the four major IgE epitopes of Pru p 3 being shared by nsLTP from other botanically related fruits. These nsLTP allergens are to varying degrees resistant to heat and digestion, and sensitization may occur through the oral, inhaled or cutaneous routes. In some populations, Pru p 3 is the primary and sole sensitizing allergen, but many are poly‐sensitised both to botanically un‐related nsLTP in foods, and non‐food sources of nsLTP such as Cannabis sativa, Platanus acerifolia, (plane tree), Ambrosia artemisiifolia (ragweed) and Artemisia vulgaris (mugwort). Initially, nsLTP sensitization appeared to be limited to Mediterranean countries, however more recent studies suggest clinically relevant sensitization occurs in North Atlantic regions and also countries in Northern Europe, with nsLTP sensitisation profiles being broadly similar. Discussion These robust allergens have the potential to sensitize and provoke symptoms to a large number of plant foods, including those which are raw, cooked or processed. It is unknown why some sensitized individuals develop clinical symptoms to foods whereas others do not, or indeed what other allergens besides Pru p 3 may be primary sensitising allergens. It is clear that these allergens are also relevant in non‐Mediterranean populations and there needs to be more recognition of this. Conclusion Non‐specific LTP allergens, present in a wide variety of plant foods and pollens, are structurally robust and so may be present in both raw and cooked foods. More studies are needed to understand routes of sensitization and the world‐wide prevalence of clinical symptoms associated with sensitization to these complex allergens.

The true severity of infection due to COVID-19 is under-represented because it is based on only those who are tested. Although nucleic acid amplifications tests (NAAT) are the gold standard for COVID-19 diagnostic testing, serological assays provide better population-level SARS-CoV-2 prevalence estimates. Implementing large sero-surveys present several logistical challenges within Canada due its unique geography including rural and remote communities. Dried blood spot (DBS) sampling is a practical solution but comparative performance data on SARS-CoV-2 serological tests using DBS is currently lacking. Here we present test performance data from a well-characterized SARS-CoV-2 DBS panel sent to laboratories across Canada representing 10 commercial and 2 in-house developed tests for SARS-CoV-2 antibodies. Three commercial assays identified all positive and negative DBS correctly corresponding to a sensitivity, specificity, positive predictive value, and negative predictive value of 100% (95% CI = 72.2, 100). Two in-house assays also performed equally well. In contrast, several commercial assays could not achieve a sensitivity greater than 40% or a negative predictive value greater than 60%. Our findings represent the foundation for future validation studies on DBS specimens that will play a central role in strengthening Canada’s public health policy in response to COVID-19.

The coronavirus disease (COVID‐19) has spread worldwide since early 2020, and there are still no signs of resolution. The Japanese Clinical Practice Guidelines for the Management of Sepsis and Septic Shock (J‐SSCG) 2020 Special Committee created the Japanese rapid/living recommendations on drug management for COVID‐19 using the experience of creating the J‐SSCGs. The Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) approach was used to determine the certainty of the evidence and strength of the recommendations. The first edition of this guideline was released on 9 September, 2020, and this document is the revised edition (version 3.1) (released 30 March, 2021). Clinical questions (CQs) were set for the following seven drugs: favipiravir (CQ1), remdesivir (CQ2), hydroxychloroquine (CQ3), corticosteroids (CQ4), tocilizumab (CQ5), ciclesonide (CQ6), and anticoagulants (CQ7). Favipiravir is recommended for patients with mild COVID‐19 not requiring supplemental oxygen (GRADE 2C); remdesivir for moderate COVID‐19 patients requiring supplemental oxygen/hospitalization (GRADE 2B). Hydroxychloroquine is not recommended for all COVID‐19 patients (GRADE 1B). Corticosteroids are recommended for moderate COVID‐19 patients requiring supplemental oxygen/hospitalization (GRADE 1B) and severe COVID‐19 patients requiring ventilator management/intensive care (GRADE 1A); however, their use is not recommended for mild COVID‐19 patients not requiring supplemental oxygen (GRADE 1B). Tocilizumab is recommended for moderate COVID‐19 patients requiring supplemental oxygen/hospitalization (GRADE 2B). Anticoagulant therapy is recommended for moderate COVID‐19 patients requiring supplemental oxygen/hospitalization and severe COVID‐19 patients requiring ventilator management/intensive care (GRADE 2C). We hope that these clinical practice guidelines will aid medical professionals involved in the care of COVID‐19 patients.

Aim This study aimed to clarify whether the lying‐flat position from prehospital to emergency department settings more effectively improves neurological outcomes of patients suspected with acute stroke over the sitting‐up position. Methods We searched PubMed, the Cochrane Central Register of Controlled Trials, and Igaku Chuo Zasshi for published randomized controlled trials until September 2019. The study population included patients suspected with acute stroke from prehospital to emergency department settings. We compared outcomes between the lying‐flat position and sitting‐up position groups. The critical outcome was the modified Rankin Scale score at 90 days, and important composite outcomes were 90‐day mortality, pneumonia recurrence, and recurrent ischemic stroke. The certainty of evidence of the outcome level was compared using the Grading of Recommendations Assessment, Development, and Evaluation approach. Results In total, 881 studies were identified from the databases, and two randomized controlled trials were included in the analysis. The pooled risk ratio of 90‐day modified Rankin Scale score was not statistically significant (risk ratio 0.86; 95% confidence interval [CI] 0.56–1.32) between the lying‐flat position and sitting‐up position groups. When comparing the 90‐day mortality, pneumonia occurrence, and recurrent ischemic stroke, no significant differences were observed between the two groups. Risk ratio was 1.00 (95% CI 0.87–1.14), 0.90 (95% CI 0.74–1.11), and 0.81 (95% CI 0.14–4.64) for 90‐day mortality, pneumonia occurrence, and recurrent ischemic stroke, respectively. Conclusion This study suggests that the lying‐flat position is not more effective than the sitting‐up position in terms of 90‐day modified Rankin Scale score in patients suspected with acute stroke.

Records and information management (RIM) professionals ensure that information flows seamlessly through organizations, thereby increasing worker productivity and facilitating the growth of the business. Yet, these professionals are often overlooked or confused with IT, archivists, secretaries, or mailroom workers. This article contends that the lack of awareness about this profession stems from the absence of a formalized educational pathway for people to become RIM professionals. Drawing on data from a comprehensive online survey, this article argues that RIM education is best suited as an independent discipline within library and information science programs.

The practice of including online discussion posts to traditional courses is increasing. Online discussions allow for active learning to occur as students express their ideas and respond to others. The time and thought provided by online discussion posts allows students to utilize higher level cognitive skills. Web-based assessments are another technology tool that instructors are including in their courses. This study examined the impact of online discussion posts on achievement of web-based assessments for an upper level undergraduate business and technology writing intensive course. Using a treatment group and a control group, student achievement scores for the online assessments were measured. Results indicate that assessed grades of the treatment groups were higher than the control group, however statistical significance was mixed among the web assessments. The results further illustrate the need for additional research into online discussions applied to web-based assessments.

Definitions can generate actionable consensus for a given subject matter by resolving important differences in philosophy and best practices and by streamlining activities for a stronger strategic direction. Interest in the global dimensions of oral health, a generally neglected area of global health, is growing; yet, no previously published research has defined the term ‘global oral health.’ As such, the Global Oral Health Interest Group of the Consortium of Universities for Global Health determined a need for an introductory definition of ‘global oral health’ to guide program planning, implementation, and evaluation. With the oversight of an expert senior Task Force for the Definition of Global Oral Health, we employed a mixed-methods approach using the more common expert consensus-building Delphi technique combined with the lesser utilized Q methodology. This approach allowed us to identify the interconnectedness of global oral health themes and integrate multiple, seemingly disparate, topics into a single streamlined concept. Our resulting definition is as follows: Global Oral Health aims for optimal oral health for all people and elimination of global health inequities through health promotion, disease prevention, and appropriate oral care approaches that consider common determinants and solutions and acknowledge oral health as part of overall health. The purpose of this short communication is to generate a narrative around our proposed definition of global oral health to support establishing guidelines and developing best practices for academic global oral health programs, policies, and practices that aim to achieve a goal of oral health globally.

Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver and is a leading cause of mortality worldwide. While there are many risk factors for HCC including alcohol, obesity, and diabetes, hepatitis B virus (HBV) and hepatitis C virus (HCV) infection still account for the majority of HCC worldwide. Globally, HBV is the leading risk factor for HCC. Patients with chronic hepatitis B (CHB) and advanced liver disease are at high risk for HCC. Screening for HCC is done routinely with ultrasound with or without alpha-fetoprotein (AFP) at six-month intervals. The combination of ultrasound and AFP has been shown to provide some additional detection of 6–8% of cases compared to ultrasound alone; however, this also increases false-positive results. This is because AFP can be elevated not only in the setting of HCC, but also in chronic hepatitis, liver cirrhosis, or ALT flare in CHB, which limits the specificity of AFP. AFP-L3 is a subfraction of AFP that is produced by malignant hepatocytes. The ratio of AFP-L3 to total AFP is reported as a percentage, and over 10% AFP-L3 is consistent with a diagnosis of HCC. Here, we review five cases of patients with CHB, cirrhosis, and HCC, and their levels of AFP and the AFP-L3% at various stages of disease including ALT flare, cirrhosis, initial diagnosis of HCC, and recurrence of HCC. These cases emphasize the utility of AFP-L3% in identifying early, new or recurrent HCC prior to the presence of imaging findings.

Sunflower is an important oilseed crop in which the biochemical pathways leading to seed oil synthesis and accumulation have been widely studied. However, how these pathways are regulated is less well understood. The WRINKLED1 (WRI1) transcription factor is considered a key regulator in the control of triacylglycerol biosynthesis, acting through the AW box binding element (CNTNG(N)7CG). Here, we identified the sunflower WRI1 gene and characterized its activity in electrophoretic mobility shift assays. We studied its role as a co-regulator of sunflower genes involved in plastidial fatty acid synthesis. Sunflower WRI1-targets included genes encoding the pyruvate dehydrogenase complex, the α-CT and BCCP genes, genes encoding ACPs and the fatty acid synthase complex, together with the FATA1 gene. As such, sunflower WRI1 regulates genes involved in seed plastidial fatty acid biosynthesis in a coordinated manner, establishing a WRI1 push and pull strategy that drives oleic acid synthesis for its export into the cytosol. We also determined the base bias at the N positions in the active sunflower AW box motif. The sunflower AW box is sequence-sensitive at the non-conserved positions, enabling WRI1-binding. Moreover, sunflower WRI1 could bind to a non-canonical AW-box motif, opening the possibility of searching for new target genes.

The cardiovascular care of cancer patients (cardio-oncology) has emerged as a new discipline in clinical medicine, given recent advances in cancer therapy, and is driven by the cardiovascular complications that occur as a direct result of cancer therapy. Traditional therapies such as anthracyclines and radiation have been recognized for years to have cardiovascular complications. Less expected were the cardiovascular effects of targeted cancer therapies, which were initially thought to be specific to cancer cells and would spare any adverse effects on the heart. Cancers are typically driven by mutations, translocations, or overexpression of protein kinases. The majority of these mutated kinases are tyrosine kinases, though serine/threonine kinases also play key roles in some malignancies. Several agents were developed to target these kinases, but many more are in development. Major successes have been largely restricted to agents targeting human epidermal growth factor receptor-2 (mutated or overexpressed in breast cancer), BCR-ABL (chronic myelogenous leukemia and some cases of acute lymphoblastic leukemia), and c-Kit (gastrointestinal stromal tumor). Other agents targeting more complex malignancies, such as advanced solid tumors, have had successes, but have not extended life to the degree seen with chronic myelogenous leukemia. Years before the first targeted therapy, Judah Folkman correctly proposed that to address solid tumors one had to target the inherent neoangiogenesis. Unfortunately, emerging evidence confirms that angiogenesis inhibitors cause cardiac complications, including hypertension, thrombosis, and heart failure. And therein lies the catch-22. Nevertheless, cardio-oncology has the potential to be transformative as the human cardiomyopathies that arise from targeted therapies can provide insights into the normal function of the heart.