Miracle-dz/UniFAR-FTUs huggingface dataset:
The COVID-19 pandemic: a threat to antimicrobial resistance containment

As of 23 April 2021, the outbreak of COVID-19 claimed around 150 million confirmed cases with over 3 million deaths worldwide. Yet, an even more serious but silent pandemic, that of antimicrobial resistance (AMR), is likely complicating the outcome of COVID-19 patients. This study discusses the current knowledge on the emergence of the SARS-CoV-2 and highlights the likely contribution of the COVID-19 pandemic on the escalation of AMR. COVID-19 engenders extensive antibiotic overuse and misuse, and will undoubtedly and substantially increase AMR rates worldwide. Amid the expanding COVID-19 pandemic, policymakers should consider the hidden threat of AMR much more, which may well be enhanced through improper use of antibiotics to treat patients with severe COVID-19 infection.
How to ask: Surveying nursing directors of nursing homes

Nursing home research may involve eliciting information from managers, yet response rates for Directors of Nursing have not been recently studied. As a part of a more extensive study, we surveyed all nursing homes in three states in 2018 and 2019, updating how to survey these leaders effectively. We focus on response rates as a measure of non‐response error and comparison of nursing home's characteristics to their population values as a measure of representation error.
Postintubation Decline in Oxygen Saturation Index Predicts Mortality in COVID-19: A Retrospective Pilot Study

Background Acute respiratory failure from COVID-19 pneumonia is a major cause of death after SARS-CoV-2 infection. We investigated whether PaO2/FiO2, oxygenation index (OI), SpO2/FiO2, and oxygen saturation index (OSI), commonly used to assess the severity of acute respiratory distress syndrome (ARDS), can predict mortality in mechanically ventilated COVID-19 patients. Methods In this single-centered retrospective pilot study, we enrolled 68 critically ill mechanically ventilated adult patients with confirmed COVID-19. Physiological variables were recorded on the day of intubation (day 0) and postintubation days 3 and 7. The association between physiological parameters, PaO2/FiO2, OI, SpO2/FiO2, and OSI with mortality was assessed using multiple variable logistic regression analysis. Receiver operating characteristic analysis was conducted to evaluate the performance of the predictive models. Results The ARDS severity indices were not statistically different on the day of intubation, suggesting similar baseline conditions in nonsurviving and surviving patients. However, these indices were significantly worse in the nonsurviving as compared to surviving patients on postintubation days 3 and 7. On intubation day 3, PaO2/FiO2 was 101.0 (61.4) in nonsurviving patients vs. 140.2 (109.6) in surviving patients, p=0.004, and on day 7 106.3 (94.2) vs. 178.0 (69.3), p < 0.001. OI was 135.0 (129.7) in nonsurviving vs. 84.8 (86.1) in surviving patients (p=0.003) on day 3 and 150.0 (118.4) vs. 61.5 (46.7) (p < 0.001) on day 7. OSI was 12.0 (11.7) vs. 8.0 (10.0) (p=0.006) on day 3 and 14.7 (13.2) vs. 6.5 (5.4) (p < 0.001) on day 7. Similarly, SpO2/FiO2 was 130 (90) vs. 210 (90) (p=0.003) on day 3 and 130 (90) vs. 230 (50) (p < 0.001) on day 7, while OSI was 12.0 (11.7) vs. 8.0 (10.0) (p=0.006) on day 3 and 14.7 (13.2) vs. 6.5 (5.4) (p < 0.001) on day 7 in the nonsurviving and surviving patients, respectively. All measures were independently associated with hospital mortality, with significantly greater odds ratios observed on day 7. The area under the receiver operating characteristic curve (AUC) for mortality prediction was greatest on intubation day 7 (AUC = 0.775, 0.808, and 0.828 for PaO2/FiO2, OI, SpO2/FiO2, and OSI, respectively). Conclusions Decline in oxygenation indices after intubation is predictive of mortality in COVID-19 patients. This time window is critical to the outcome of these patients and a possible target for future interventions. Future large-scale studies to confirm the prognostic value of the indices in COVID-19 patients are warranted.
Impact of Different Approaches to Preparing Notes for Analysis With Natural Language Processing on the Performance of Prediction Models in Intensive Care

Supplemental Digital Content is available in the text. OBJECTIVES: To evaluate whether different approaches in note text preparation (known as preprocessing) can impact machine learning model performance in the case of mortality prediction ICU. DESIGN: Clinical note text was used to build machine learning models for adults admitted to the ICU. Preprocessing strategies studied were none (raw text), cleaning text, stemming, term frequency-inverse document frequency vectorization, and creation of n-grams. Model performance was assessed by the area under the receiver operating characteristic curve. Models were trained and internally validated on University of California San Francisco data using 10-fold cross validation. These models were then externally validated on Beth Israel Deaconess Medical Center data. SETTING: ICUs at University of California San Francisco and Beth Israel Deaconess Medical Center. SUBJECTS: Ten thousand patients in the University of California San Francisco training and internal testing dataset and 27,058 patients in the external validation dataset, Beth Israel Deaconess Medical Center. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Mortality rate at Beth Israel Deaconess Medical Center and University of California San Francisco was 10.9% and 7.4%, respectively. Data are presented as area under the receiver operating characteristic curve (95% CI) for models validated at University of California San Francisco and area under the receiver operating characteristic curve for models validated at Beth Israel Deaconess Medical Center. Models built and trained on University of California San Francisco data for the prediction of inhospital mortality improved from the raw note text model (AUROC, 0.84; CI, 0.80–0.89) to the term frequency-inverse document frequency model (AUROC, 0.89; CI, 0.85–0.94). When applying the models developed at University of California San Francisco to Beth Israel Deaconess Medical Center data, there was a similar increase in model performance from raw note text (area under the receiver operating characteristic curve at Beth Israel Deaconess Medical Center: 0.72) to the term frequency-inverse document frequency model (area under the receiver operating characteristic curve at Beth Israel Deaconess Medical Center: 0.83). CONCLUSIONS: Differences in preprocessing strategies for note text impacted model discrimination. Completing a preprocessing pathway including cleaning, stemming, and term frequency-inverse document frequency vectorization resulted in the preprocessing strategy with the greatest improvement in model performance. Further study is needed, with particular emphasis on how to manage author implicit bias present in note text, before natural language processing algorithms are implemented in the clinical setting.
Influencing Factors of Outpatients’ Satisfaction in China a Cross-Sectional Study of 16 Public Tertiary Hospitals

Purpose This study aimed to analyze the status of patient satisfaction in outpatients of tertiary hospitals and the factors affecting patient satisfaction, in order to provide a scientific basis for improving patient satisfaction. Methods A total of 6480 surveys of outpatients were conducted by a cross-sectional study in 16 tertiary hospitals in the Zhejiang province of China. The main contents of the survey were the basic characteristics of patients. Statistical description, single-factor analysis and binary logistic regression analysis were used to screen influencing factors. Results Results of this study showed that the total satisfaction score of outpatients was 87.13±13.47, and higher scored factors in the survey factors were nursing level, the convenience of registration and convenience of appointment diagnosis and treatment. The factors with lower scores were treatment effect, environmental sanitation and comfort and other staffs’ attitudes. Hospital managers should pay attention to the improvement of treatment level, environmental sanitation and comfort and other staffs’ attitudes. Conclusion In the process of serving outpatients, doctors should pay more attention to patients who are male, 31–45 years old or over 60 years old, permanent residents, from public institutions, possessed postgraduate education, without medical insurance, and who visiting paediatrics and Chinese medicine hospitals.
Courtesy Authorship Practices Among First and Senior Authors

Supplemental Digital Content is available in the text Objectives: A courtesy author is an individual who has not met authorship criteria but is listed as an author. This practice is common and often seen as victimless. Because publications are used for funding and promotion decisions, it is critical to understand biases in this practice. Methods: An anonymous survey was conducted from March to October 2020 of first and senior authors of publications from 2014 to 2015 in 8 surgical journals. Authors were surveyed about demographic data, practice setting, and courtesy author practices. Results: Three hundred forty-one authors responded (16% response rate). 75% were from academic practice settings. 14% reported adding courtesy authors 5 or more times in the past year. Courtesy authors were more often male (80%, P = 0.023), older (75%), and of higher academic rank (65%) than first/senior authors. All author groups were >75% white. When a reason was reported, 46% added a courtesy author due to avoid retaliation; 64% to avoid awkwardness. 26% expected reciprocal authorship offers. 92% of respondents acknowledge understanding International Committee of Medical Journal Editors authorship criteria. Women were less common among those added from goodwill than those added from fear (P = 0.039.) When courtesy authors were of a lower rank than first/senior authors, they were nearly twice as likely to be female (P = 0.0056) or non-white (P = 0.0184.) Conclusion: Courtesy authors were more often male, older, and higher rank than first/senior authors. Fear of career consequences was a major motivator for including courtesy authors. Understanding the motivations and pressures leading to courtesy authorship will help to correct this practice.
Differential Proximity of Perisynaptic Astrocytic Best1 at the Excitatory and Inhibitory Tripartite Synapses in APP/PS1 and MAOB-KO Mice Revealed by Lattice Structured Illumination Microscopy

Bestrophin-1 (Best1) is a GABA- and glutamate-permeable, Ca2+-activated Cl- channel, which is mainly expressed in astrocytes and localized at the microdomain or perisynaptic junction of the tripartite synapse. Distribution of Best1 is dramatically changed in pathological conditions such as Alzheimer’s disease. However, it is still unknown whether Best1 is located at the glutamatergic or GABAergic tripartite synapses. Here, we utilized the Lattice structured illumination microscopy (Lattice SIM) to visualize Best1 expression at the perisynaptic junctions of the tripartite synapses in CA1 of mouse hippocampus. We performed co-labeling with antibodies against 1) Best1 and vesicular glutamate transporter-2 (vGLUT2) or 2) Best1 and vesicular GABA transporter (vGAT) to measure the proximity of Best1-containing perisynapse to glutamatergic or GABAergic presynapse, respectively. In addition, we examined two transgenic mouse lines of 1) APP/PS1 mouse showing high astrocytic MAOB activity and cytosolic GABA and 2) MAOB-KO mouse showing low astrocytic GABA. Lattice SIM images were further processed by Imaris, which allowed 3D-rendering and spot identification. We found that astrocytic Best1 was distributed closer to the glutamatergic synapses than GABAergic synapses in the wild-type mice. In APP/PS1 mice, Best1 distribution was significantly changed by moving away from the glutamatergic synapses while moving closer to the GABAergic synapses. On the contrary, in MAOB-KO mice, the Best1 distribution was dramatically changed by moving closer to the glutamatergic synapses and moving far away from the GABAergic synapses. Our findings propose that the proximity of Best1-containing perisynapses to presynapses dynamically changes according to the level of astrocytic cytosolic GABA.
Specific Interaction of DDX6 with an RNA Hairpin in the 3′ UTR of the Dengue Virus Genome Mediates G1 Phase Arrest

Dengue virus (DENV) is transmitted by mosquitoes to humans, infecting 390 million individuals per year globally. About 20% of infected patients shows a spectrum of clinical manifestation, ranging from a mild flu-like syndrome, to dengue fever, to life-threatening severe dengue diseases, including dengue hemorrhagic fever and dengue shock syndrome. ABSTRACT The extent to which viral genomic RNAs interact with host factors and contribute to host response and disease pathogenesis is not well known. Here, we report that the human RNA helicase DDX6 specifically binds to the viral most conserved RNA hairpin in the A3 element in the dengue 3′ UTR, with nanomolar affinities. DDX6 CLIP confirmed the interaction in HuH-7 cells infected by dengue virus serotype 2. This interaction requires three conserved residues—Lys307, Lys367, and Arg369—as well as the unstructured extension in the C-terminal domain of DDX6. Interestingly, alanine substitution of these three basic residues resulted in RNA-independent ATPase activity, suggesting a mechanism by which RNA-binding and ATPase activities are coupled in DEAD box helicases. Furthermore, we applied a cross-omics gene enrichment approach to suggest that DDX6 is functionally related to cell cycle regulation and viral pathogenicity. Indeed, infected cells exhibited cell cycle arrest in G1 phase and a decrease in the early S phase. Exogenous expression of intact DDX6, but not A3-binding-deficient mutants, alleviated these effects by rescue of the DNA preinitiation complex expression. Disruption of the DDX6-binding site was found in dengue and Zika live-attenuated vaccine strains. Our results suggested that dengue virus has evolved an RNA aptamer against DDX6 to alter host cell states and defined DDX6 as a new regulator of G1/S transition. IMPORTANCE Dengue virus (DENV) is transmitted by mosquitoes to humans, infecting 390 million individuals per year globally. About 20% of infected patients shows a spectrum of clinical manifestation, ranging from a mild flu-like syndrome, to dengue fever, to life-threatening severe dengue diseases, including dengue hemorrhagic fever and dengue shock syndrome. There is currently no specific treatment for dengue diseases, and the molecular mechanism underlying dengue pathogenesis remains poorly understood. In this study, we combined biochemical, bioinformatics, high-content analysis and RNA sequencing approaches to characterize a highly conserved interface of the RNA genome of DENV with a human factor named DDX6 in infected cells. The significance of our research is in identifying the mechanism for a viral strategy to alter host cell fates, which conceivably allows us to generate a model for live-attenuated vaccine and the design of new therapeutic reagent for dengue diseases.
Characteristics of systematic reviews evaluating treatments for COVID-19 registered in PROSPERO

Abstract Characteristics and research collaboration of registered systematic reviews (SRs) on treatment modalities for coronavirus disease-2019 (COVID-19) remain unclear. This study analysed research collaboration, interventions and outcome measures in registered SRs on COVID-19 treatments and pointed out the relevant problems. PROSPERO (international prospective register of systematic reviews) was searched for SRs on COVID-19 treatments as of 2 June 2020. Excel 2016 was used for descriptive analyses of the extracted data. VOSviewer 1.6. 14 software was used to generate network maps for collaborations between countries and institutions. A total of 189 SRs were included, which were registered by 301 institutions from 39 countries. China (69, 36.50%) exhibited the highest output. Cooperation between countries was not close enough. As an institution, the Chengdu University of Traditional Chinese Medicine (7, 3.70%) had the highest output. There was close cooperation between institutions. Interventions included antiviral therapy (81, 42.86%), respiratory support (16, 8.47%), circulatory support (11, 5.82%), plasma therapy for convalescent patients (11, 5.82%), immunotherapy (9, 4.76%), TCM (traditional Chinese medicine) treatment (9, 4.76%), rehabilitation treatment (5, 2.65%), anti-inflammatory treatment (16, 8.47%) and other treatments (31, 16.40%). Concerning antiviral therapy (81, 42.86%), the most commonly used antiviral agents were chloroquine/hydroxychloroquine (26, 13.76%), followed by remdesivir (12, 6.35%), lobinavir/ritonavir (11, 5.82%), favipiravir (5, 2.65%), ribavirin (5, 2.65%), interferon (5, 2.65%), abiron (4, 2.12%) and abidor (4, 2.12%). The most frequently used primary and secondary outcomes were the mortality rate (92, 48.68%) and hospital stay length (48, 25.40%), respectively. The expression of the outcomes was not standardised. Many COVID-19 SRs on treatment modalities have been registered, with a low completion rate. Although there was some collaboration between countries and institutions in the currently registered SRs on treatment modalities for COVID-19 on PROSPERO, cooperation between countries should be further enhanced. More attention should be directed towards identifying deficiencies of outcome measures, and the standardisation of results should be maximised.
Registered report: Age-preserved semantic memory and the CRUNCH effect manifested as differential semantic control networks: an fMRI study

Semantic memory representations are generally well maintained in aging, whereas semantic control is thought to be more affected. To explain this phenomenon, this study tested the predictions of the Compensation-Related Utilization of Neural Circuits Hypothesis (CRUNCH), focusing on task demands in aging as a possible framework. The CRUNCH effect would manifest itself in semantic tasks through a compensatory increase in neural activation in semantic control network regions but only up to a certain threshold of task demands. This study compares 39 younger (20–35 years old) with 39 older participants (60–75 years old) in a triad-based semantic judgment task performed in an fMRI scanner while manipulating task demand levels (low versus high) through semantic distance. In line with the CRUNCH predictions, differences in neurofunctional activation and behavioral performance (accuracy and response times) were expected in younger versus older participants in the low-versus high-demand conditions, which should be manifested in semantic control Regions of Interest (ROIs). Our older participants had intact behavioral performance, as proposed in the literature for semantic memory tasks (maintained accuracy and slower response times (RTs)). Age-invariant behavioral performance in the older group compared to the younger one is necessary to test the CRUNCH predictions. The older adults were also characterized by high cognitive reserve, as our neuropsychological tests showed. Our behavioral results confirmed that our task successfully manipulated task demands: error rates, RTs and perceived difficulty increased with increasing task demands in both age groups. We did not find an interaction between age group and task demand, or a statistically significant difference in activation between the low- and high-demand conditions for either RTs or accuracy. As for brain activation, we did not find the expected age group by task demand interaction, or a significant main effect of task demand. Overall, our results are compatible with neural activation in the semantic network and the semantic control network, largely in frontotemporoparietal regions. ROI analyses demonstrated significant effects (but no interactions) of task demand in the left and right inferior frontal gyrus, the left posterior middle temporal gyrus, the posterior inferior temporal gyrus and the prefrontal gyrus. Overall, our test did not confirm the CRUNCH predictions.
Taking a BiTE out of the CAR T space race

Chimaeric antigen receptor T‐cell (CAR T) therapy has evolved at an exponential pace and seeks to revolutionize the CAR T space with next‐generation CARs and expanding indications in plasma cell dyscrasias. Recent developments in Bispecific T‐cell engager therapy (BiTEs) may level the playing field with CAR T therapy, offering key advantages with off‐the‐shelf or on‐demand treatment and a manageable toxicity profile to encompass a wider pool of eligible patients in the outpatient setting. The coexistence of both modalities will remain important in overall management and accelerate the next iteration of both cellular and BiTEs. This article summarises the current progress, potential future of both therapies for haematologic malignancies, and their economic implications on the healthcare system.
A Resident-Led Intervention to Increase Initiation of Buprenorphine Maintenance for Hospitalized Patients With Opioid Use Disorder.

BACKGROUND Hospitalized patients with opioid use disorder (OUD) are rarely started on buprenorphine or methadone maintenance despite evidence that these medications reduce all-cause mortality, overdoses, and hospital readmissions. OBJECTIVE To assess whether clinician education and a team of residents and hospitalist attendings waivered to prescribe buprenorphine increased the rate of starting patients with OUD on buprenorphine maintenance. DESIGN, SETTING, AND PARTICIPANTS Quality improvement study conducted at a large, urban, academic hospital in Maryland involving hospitalized patients with OUD on internal medicine resident services. INTERVENTION We developed a protocol for initiating buprenorphine maintenance, presented an educational conference, and started the resident-led Buprenorphine Bridge Team of residents and attendings waivered to prescribe buprenorphine to bridge patients from discharge to follow-up. MEASUREMENTS The percent of eligible inpatients with OUD initiated on buprenorphine maintenance, 24 weeks before and after the intervention; engagement in treatment after discharge; and resident knowledge and comfort with buprenorphine. RESULTS The rate of starting buprenorphine maintenance increased from 10% (30 of 305 eligible patients) to 24% (64 of 270 eligible patients) after the intervention, with interrupted time series analysis showing a significant increase in rate (14.4%; 95% CI, 3.6%-25.3%; P = .02). Engagement in treatment after discharge was unchanged (40%-46% engaged 30 days after discharge). Of 156 internal medicine residents, 89 (57%) completed the baseline survey and 66 (42%) completed the follow-up survey. Responses demonstrated improved resident knowledge and comfort with buprenorphine. CONCLUSION Internal medicine resident teams were more likely to start patients on buprenorphine maintenance after clinician education and implementation of a Buprenorphine Bridge Team.