bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dissecting Human Antibody Responses: Useful, Basic, and Surprising Findings
Authors: Lanzavecchia Antonio 
Published: April 2021

Abstract
We use cell culture-based high-throughput methods to interrogate human memory B cell and plasma cell repertoires and to isolate antibodies selected on the basis of their neutralizing potency and breadth. Relevant examples are antibodies that neutralize all influenza A viruses or even four paramyxoviruses. By targeting conserved structures, these broadly neutralizing antibodies are less prone to select escape mutants and are promising candidates for prophylaxis and therapy of infections, as well as tools for vaccine design. The value of a target-agnostic approach to vaccine design is illustrated by our discovery of extremely potent antibodies that neutralize human cytomegalovirus, which led to the identification of their viral ligand, a pentameric complex that was then produced and tested as an effective vaccine. By reconstructing the genealogy trees of specific B cell clones, we investigate the role of somatic mutations in affinity maturation and in generation of antibody variants with broader or different specificity. Somatic mutations can also generate autoantibodies, as found in patients with pemphigus and autoimmune pulmonary alveolar proteinosis. Recently, while searching for antibodies that broadly react with malaria variant antigens, we discovered a new mechanism of antibody diversification, which relies on templated insertions of genomic DNA sequences into immunoglobulin genes, followed by somatic mutations.

Disclosures
Lanzavecchia: Humabs SA: Equity Ownership, Research Funding.
DNA Methylation in Cancer and Development: An Evolving Paradigm
Authors: Figueroa Maria E. 
Published: April 2021

DNA methylation is an epigenetic mark which, in mammals, occurs primarily on position 5 of cytosines, especially at those found in the context of CpG dinucleotides. This CpG methylation is known to play a major role in gene regulation. Cytosine methylation is regulated by the DNA methyltransferases, responsible for adding the methyl group to unmethylated CpGs, and the TET dioxygenases, involved in the DNA demethylation pathway. Initially, DNA methylation was believed to be important mainly for gene silencing through promoter DNA methylation, especially at CpG-rich promoters containing CpG islands. However, our understanding of the role that DNA methylation plays in gene regulation during normal development and how this process becomes deregulated in cancer, has evolved in recent years. Moreover, the discovery of frequent mutations in DNMT3A and TET2 both in clonal hematopoiesis of indeterminate significance as well as in many hematological malignancies has brought new interest into understanding what role DNA methylation plays in normal HSC function as well as how it contributes to malignant transformation. In this session, we will review the current understanding in the field of DNA methylation and gene regulation, and present data on DNA methylation in normal HSCs as well as the role that this epigenetic mark plays during leukemic transformation in acute myeloid leukemia.

Disclosures
No relevant conflicts of interest to declare.
Effect of intermittent isometric handgrip exercise protocol with short exercise duration on cognitive performance
Authors: Saito Shotaro , Washio Takuro , Watanabe Hironori , Ando Soichi , Ogoh Shigehiko 
Published: April 2021

AbstractThe handgrip exercise, a small muscle exercise, is useful for exercise therapy, particularly in the elderly and bedridden patients. The isometric handgrip (IHG) exercise has been utilized in training programs to reduce resting blood pressure; however, the acute effects of the IHG exercise on cognitive performance are not fully understood. The present study aimed to investigate the effect of an intermittent IHG exercise protocol with short exercise duration, which minimizes the arterial blood pressure response to exercise, on cognitive performance. Twenty-two young healthy subjects performed the intermittent IHG exercise protocol, which consisted of 30-s IHG and 45-s recovery × 16 trials; the exercise intensity of the IHG exercise was 30% of the maximal voluntary contraction. Cognitive performance was evaluated before and after the exercise with the Go/No-Go and memory recognition tasks. Specifically, the reaction time (RT) and performance accuracy were measured. The intermittent IHG exercise protocol did not change the RT or performance accuracy of either the Go/No-Go task (P = 0.222 and P = 0.260, respectively) or the memory recognition task (P = 0.427 and P = 0.245, respectively). These findings suggest that the intermittent IHG exercise protocol with short exercise duration may not provide enough stimulation to improve cognitive performance despite being useful as a safe exercise therapy in the elderly and in patients with cardiovascular disease.
Establishing a consensus for the hallmarks of cancer based on gene ontology and pathway annotations
Authors: Chen Yi , Verbeek Fons. J. , Wolstencroft Katherine 
Published: April 2021

Abstract
Background
The hallmarks of cancer provide a highly cited and well-used conceptual framework for describing the processes involved in cancer cell development and tumourigenesis. However, methods for translating these high-level concepts into data-level associations between hallmarks and genes (for high throughput analysis), vary widely between studies. The examination of different strategies to associate and map cancer hallmarks reveals significant differences, but also consensus.

Results
Here we present the results of a comparative analysis of cancer hallmark mapping strategies, based on Gene Ontology and biological pathway annotation, from different studies. By analysing the semantic similarity between annotations, and the resulting gene set overlap, we identify emerging consensus knowledge. In addition, we analyse the differences between hallmark and gene set associations using Weighted Gene Co-expression Network Analysis and enrichment analysis.

Conclusions
Reaching a community-wide consensus on how to identify cancer hallmark activity from research data would enable more systematic data integration and comparison between studies. These results highlight the current state of the consensus and offer a starting point for further convergence. In addition, we show how a lack of consensus can lead to large differences in the biological interpretation of downstream analyses and discuss the challenges of annotating changing and accumulating biological data, using intermediate knowledge resources that are also changing over time.
Simultaneous comparison of depth of sedation performance between SedLine and BIS during general anesthesia using custom passive interface hardware: study protocol for a prospective, non-blinded, non-randomized trial
Authors: Jones James Harvey , Nittur Vinay Ravikumar , Fleming Neal , Applegate Richard L. 
Published: April 2021

Abstract
Background
Intraoperative brain function monitoring with processed electroencephalogram (EEG) indices, such as the bispectral index (BIS) and patient state index (PSI), may improve characterization of the depth of sedation or anesthesia when compared to conventional physiologic monitors, such as heart rate and blood pressure. However, the clinical assessment of anesthetic depth may not always agree with available processed EEG indices. To concurrently compare the performance of BIS and SedLine monitors, we present a data collection system using shared individual generic sensors connected to a custom-built passive interface box.

Methods
This prospective, non-blinded, non-randomized study will enroll 100 adult American Society of Anesthesiologists (ASA) class I-III patients presenting for elective procedures requiring general anesthesia. BIS and SedLine electrodes will be placed preoperatively according to manufacturer recommendations and their respective indices tracked throughout anesthesia induction, maintenance and emergence. The concordance between processed EEG indices and clinical assessments of anesthesia depth will be analyzed with chi-square and kappa statistic.

Discussion
Prior studies comparing brain function monitoring devices have applied both sensors on the forehead of study subjects simultaneously. With limited space and common sensor locations between devices, it is not possible to place both commercial sensor arrays according to the manufacturer’s recommendations, thus compromising the validity of these comparisons. This trial utilizes a custom interface allowing signals from sensors to be shared between BIS and SedLine monitors to provide an accurate comparison. Our results will also characterize the degree of agreement between processed EEG indices and clinical assessments of anesthetic depth as determined by the anesthesiologists’ interpretations of acute changes in blood pressure and heart rate as well as the administration, or change to the continuous delivery, of medications at these timepoints. Patient factors (such as burst suppression state or low power EEG conditions from aging brain), surgical conditions (such as use of electrocautery), artifacts (such as electromyography), and anesthesia medications and doses (such as end-tidal concentration of volatile anesthetic or hypnotic infusion dose) that lead to lack of agreement will be explored as well.

Trial registration
Clinical Trials (ClinicalTrials.gov), NCT03865316. Registered on 4 February 2019 – retrospectively registered. Sponsor: Masimo Corporation.
Effectiveness of P-wave ECG index and left atrial appendage volume in predicting atrial fibrillation recurrence after first radiofrequency catheter ablation
Authors: Li Ruibin , Yang Xiaohong , Jia Min , Wang Dong , Cui Xiaoran , Bai Long , Zhao Lei , Zhang Jidong 
Published: April 2021

Abstract
Background
The primary aim was to observe the predictive value of P-wave ECG index and left atrial appendage volume (LLAV) for atrial fibrillation recurrence after first radiofrequency catheter ablation.

Methods
A total of 196 patients with paroxysmal atrial fibrillation were enrolled. The preoperative LLAV was measured by cardiac enhanced CT. The P-wave ECG index including minimum P-wave duration (P-min), maximum P-wave duration (P-max), mean P-wave duration (mPWD), P-wave dispersion (PWD), P-wave terminal force in lead V1 (PtfV1), PR interval prolongation, and interatrial block (IAB) were analyzed and recorded in 12-lead ECG of sinus rhythm.

Results
According to the follow-up results, the patients were divided into two groups: the non-recurrence group and the recurrence group. P-min, PWD, P-max, PtfV1 ≥ 0.04 mV·s, PR interval prolongation, and the ratio of first and third-degree IAB in the recurrence group were higher than those in the non-recurrence group, with significant statistical differences (P < 0.05). Kaplan–Meier curve analysis was performed on time to atrial fibrillation recurrence after catheter ablation when PtfV1 ≥ 0.04 mv s by comparison between groups (Log Rank test: 2 = 4.739, P < 0.001). Kaplan–Meier curve analysis showed that the survival rate without recurrence of atrial fibrillation after catheter ablation was lower when the LLAV exceeded 8.0 mL (log-rank test P < 0.001).

Conclusion
PWD, P-max, PtfV1, PR interval prolongation, first and third-degree IAB, and LLAV can effectively predict atrial fibrillation recurrence after radiofrequency catheter ablation. The combination might be a valid and alternative independent predictor of recurrence.
Healthcare professional-led interventions on lifestyle modifications for hypertensive patients – a systematic review and meta-analysis
Authors: Treciokiene Indre , Postma Maarten , Nguyen Thang , Fens Tanja , Petkevicius Jurgis , Kubilius Raimondas , Gulbinovic Jolanta , Taxis Katja 
Published: April 2021

AbstractBackgroundAbout 0.9 billion people in the world have hypertension. The mortality due to hypertension increased dramatically over the last decades. Healthcare professionals should support patients with hypertension to modify their lifestyle to decrease blood pressure, but an overview of effective lifestyle interventions is lacking. The aim of this study was to determine whether healthcare professional-led interventions on lifestyle modifications are effective in lowering blood pressure in patients with hypertension.MethodsA systematic literature review following the PRISMA guidelines was conducted. PubMed, EMBASE and CINAHL databases were searched for randomized control trials (RCTs) of interventions on lifestyle modifications of hypertensive patients which were performed by healthcare professionals (physician, nurse, pharmacist) and which reported blood pressure measurements. Papers were reviewed by two reviewers and analysed using Cochrane software Revman 5.4. In a meta-analysis difference in systolic blood pressure (SBP), diastolic blood pressure (DBP) and the percentage of patients with controlled blood pressure (BP) was analysed.ResultsIn total, 34 clinical trials reporting on 22,419 patients (mean age 58.4 years, 49.14% female, 69.9% used antihypertensive medications) were included. The mean difference SBP was − 4.41 mmHg (95% CI, − 5.52to − 3.30) and the mean difference DBP was − 1.66 mmHg (95% CI − 2.44 to − 0.88) in favor of the intervention group vs usual care. Fifty-six percent of patients achieved BP control in the intervention group vs 44% in usual care, OR = 1.87 (95% CI, 1.51 to 2.31).ConclusionHealthcare professional-led interventions were effective. Patients achieved almost 5 mmHg decrease of SBP and more patients achieved BP control. The results suggest that efforts are needed for widespread implementation.
Exploring the effect of professional experience on knowledge towards geriatric care among nurses working in adult care units
Authors: Amsalu Erkihun Tadesse , Messele Tesfaye Alemayehu , Adane Metadel 
Published: April 2021

Abstract
Background
The elder population suffered from social, economic, and health (which includes physical) related problems. Thus, these problems are complex and interrelated, thereby requiring specific knowledge and expertise to meet them. However, there were limited researches previously done to explore nurse’s knowledge towards geriatric care. Therefore, this study aimed to assess knowledge towards geriatric care and to examine its predictors in North east Ethiopia. The findings will be helpful to develop strategies that would promote nurses’ knowledge, which in turn improves the quality of patient care and consequently, the health of older people.

Methods
A facility-based cross-sectional study was conducted from March 8 to 28, 2020, among 335 nurses. Simple random sampling technique was employed to select study participants. A structured self-administered questionnaire was used to collect data on knowledge of nurses towards older adult care. A multivariable logistic regression model was applied to identify significant predictors and P-value< 0.05 was used to declare the significance of association.

Results
In the study, a total of 335 nurses participated. About 192(57.3%) of them had poor knowledge towards older adult care. Thus, level of education (AOR = 1.9, 95%CI: 1.1–3.2), year of experience 1–5 year (AOR = 2.7, 95%CI: 1.5–4.9), 5–10 years (AOR = 2.5, 95%CI: 1.4–4.4), and previously living with older adult at home (AOR = 1.6, 95%CI: 1.05–2.7) were significant predictors of knowledge on older adult care.

Conclusions
Our study showed; most of nurses had poor knowledge of the care of elder patients. Level of education, level of experience, and lived with the older adult were factors that contributed for poor knowledge. Thus, professional organizations should focus on changing nursing curricula and providing professional development workshops to improve the knowledge of nurses on geriatric care.
Diagnostic performance of the combined nasal and throat swab in patients admitted to hospital with suspected COVID-19
Authors:   on behalf of the DataLoch COVID-19 Collaboration, Lee Kuan Ken , Doudesis Dimitrios , Ross Daniella A. , Bularga Anda , MacKintosh Claire L. , Koch Oliver , Johannessen Ingolfur , Templeton Kate , Jenks Sara , Chapman Andrew R. , Shah Anoop S. V. , Anand Atul , Perry Meghan R. , Mills Nicholas L. 
Published: April 2021

Abstract
Background
Accurate diagnosis in patients with suspected coronavirus disease 2019 (COVID-19) is essential to guide treatment and limit spread of the virus. The combined nasal and throat swab is used widely, but its diagnostic performance is uncertain.

Methods
In a prospective, multi-centre, cohort study conducted in secondary and tertiary care hospitals in Scotland, we evaluated the combined nasal and throat swab with reverse transcriptase-polymerase chain reaction (RT-PCR) for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in consecutive patients admitted to hospital with suspected COVID-19. Diagnostic performance of the index and serial tests was evaluated for a primary outcome of confirmed or probable COVID-19, and a secondary outcome of confirmed COVID-19 on serial testing. The diagnosis was adjudicated by a panel, who recorded clinical, laboratory and radiological features blinded to the test results.

Results
We enrolled 1368 consecutive patients (median age 68 [interquartile range, IQR 53–80] years, 47% women) who underwent a total of 3822 tests (median 2 [IQR 1–3] tests per patient). The primary outcome occurred in 36% (496/1368), of whom 65% (323/496) and 35% (173/496) had confirmed and probable COVID-19, respectively. The index test was positive in 255/496 (51%) patients with the primary outcome, giving a sensitivity and specificity of 51.4% (95% confidence interval [CI] 48.8 to 54.1%) and 99.5% (95% CI 99.0 to 99.8%). Sensitivity increased in those undergoing 2, 3 or 4 tests to 60.1% (95% CI 56.7 to 63.4%), 68.3% (95% CI 64.0 to 72.3%) and 77.6% (95% CI 72.7 to 81.9%), respectively. The sensitivity of the index test was 78.9% (95% CI 74.4 to 83.2%) for the secondary outcome of confirmed COVID-19 on serial testing.

Conclusions
In patients admitted to hospital, a single combined nasal and throat swab with RT-PCR for SARS-CoV-2 has excellent specificity, but limited diagnostic sensitivity for COVID-19. Diagnostic performance is significantly improved by repeated testing.
Respiratory microbes detected in hospitalized adults with acute respiratory infections: associations between influenza A(H1N1)pdm09 virus and intensive care unit admission or fatal outcome in Vietnam (2015–2017)
Authors: Truong Phuong Thai , Saito Shinji , Takayama Ikuyo , Furuya Hiroyuki , Nguyen Binh Gia , Do Thanh Van , Phan Phuong Thu , Do Cuong Duy , Dao Co Xuan , Pham Thach The , Dang Tuan Quoc , Ngo Chau Quy , Le Ngan Thi , Bui Vuong Minh , Le Dung Trung , Vu Van Thi Tuong , Pham Thuy Thi Phuong , Arashiro Takeshi , Kageyama Tsutomu , Nakajima Noriko 
Published: April 2021

Abstract
Background
Acute respiratory tract infection (ARI) is a leading cause of hospitalization, morbidity, and mortality worldwide. Respiratory microbes that were simultaneously detected in the respiratory tracts of hospitalized adult ARI patients were investigated. Associations between influenza A(H1N1)pdm09 virus (H1N1pdm) detection and intensive care unit (ICU) admission or fatal outcome were determined.

Methods
This prospective observational study was conducted between September 2015 and June 2017 at Bach Mai Hospital, Hanoi, Vietnam. Inclusion criteria were hospitalized patients aged ≥15 years; one or more of symptoms including shortness of breath, sore throat, runny nose, headache, and muscle pain/arthralgia in addition to cough and fever > 37.5 °C; and ≤ 10 days from the onset of symptoms. Twenty-two viruses, 11 bacteria, and one fungus in airway specimens were examined using a commercial multiplex real-time PCR assay. Associations between H1N1pdm detection and ICU admission or fatal outcome were investigated by univariate and multivariate logistic regression analyses.

Results
The total of 269 patients (57.6% male; median age, 51 years) included 69 ICU patients. One or more microbes were detected in the airways of 214 patients (79.6%). Single and multiple microbes were detected in 41.3 and 38.3% of patients, respectively. Influenza A(H3N2) virus was the most frequently detected (35 cases; 13.0%), followed by H1N1pdm (29 cases; 10.8%). Hematological disease was associated with ICU admission (p < 0.001) and fatal outcomes (p < 0.001) using the corrected significance level (p = 0.0033). Sex, age, duration from onset to sampling, or number of detected microbes were not significantly associated with ICU admission or fatal outcomes. H1N1pdm detection was associated with ICU admission (odds ratio [OR] 3.911; 95% confidence interval [CI] 1.671–9.154) and fatal outcome (OR 5.496; 95% CI 1.814–16.653) after adjusting for the confounding factors of comorbidities, bacteria/Pneumocystis jirovecii co-detection, and age.

Conclusions
H1N1pdm was associated with severe morbidity and death in adult patients hospitalized with respiratory symptoms. The diagnosis of subtype of influenza virus may be epidemiologically important.
Neonatal systemic juvenile Xanthogranuloma with Hydrops diagnosed by Purpura skin biopsy: a case report and literature review
Authors: Uehara Yohji , Wada Yuka Sano , Iwasaki Yuka , Yoneda Kota , Ikuta Yasuhisa , Amari Shoichiro , Maruyama Hidehiko , Tsukamoto Keiko , Isayama Tetsuya , Sakamoto Kenichi , Shioda Yoko , Miyazaki Osamu , Irie Rie , Yoshioka Takako , Mochimaru Naoko , Yoshida Kazue , Ito Yushi 
Published: April 2021

Abstract
Background
Systemic juvenile xanthogranuloma is a very rare disease typically presents as skin lesions with yellow papules or nodules and is sometimes fatal. We report a case of congenital neonatal systemic juvenile xanthogranuloma with atypical skin appearance that made the diagnosis difficult.

Case presentation
A preterm Japanese female neonate with prenatally diagnosed fetal hydrops in-utero was born with purpuric lesions involving the trunk and face. Since birth, she had hypoxemic respiratory failure, splenomegaly, anemia, thrombocytopenia, coagulopathy, and was transfusion dependent for red blood cells, fresh frozen plasma, and platelets. Multiple cystic lesions in her liver, part of them with vascular, were detected by ultrasound. A liver biopsy was inconclusive. A skin lesion on her face similar to purpura gradually changed to a firm and solid enlarged non-yellow nodule. Technically, the typical finding on skin biopsy would have been histiocytic infiltration (without Touton Giant cells) and immunohistochemistry results which then would be consistent with a diagnosis of systemic juvenile xanthogranuloma, and chemotherapy improved her general condition.

Conclusions
This case report shows that skin biopsies are necessary to detect neonatal systemic juvenile xanthogranuloma when there are organ symptoms and skin eruption, even if the skin lesion does not have a typical appearance of yellow papules or nodules.