bluuebunny/crossref_metadata_2025 huggingface dataset:
Economic and Epidemiological Impact of an Improvement Plan for the Decrease of Ventilator-Associated Pneumonia in a Tertiary Hospital in Mexico
Authors: Sosa-Hernández Oscar , Matías-Téllez Bernardina , Silva-López Yefté Efraín , Alarcón-Hernández Verónica , Bello-López Juan Manuel , Cureño-Díaz Mónica Alethia , Lugo-Zamudio Gustavo Esteban
Published: May 2020

Introduction

The objective of this work is to measure the economic and epidemiological impact of the implementation of a comprehensive quality improvement plan (CQIP) for the prevention and reduction of ventilator-associated pneumonia (VAP) in the adult intensive care unit in a Mexican hospital.

Materials and Methods

A cross-sectional, ambispective, comparative, analytical, observational study was conducted with epidemiological data on cases of health care–associated infections and with information from the Hospital Epidemiological Surveillance Unit from August 2017 to July 2018.

Results

Before to the implementation of the CQIP, there were a total of 26 VAPs, with a rate of 32.2 per 1000 ventilator-days. After the implementation of CQIP, there were 14 VAPs, with a rate of 23.4 per 1000 ventilator-days, with a 46.2% decrease in incidence (P = 0.02). Before the installation of the interventions, the expense was $4,471,073.80, with an average cost per case of $171,964.38. The total cost per bed-day in the adult intensive care unit was $331,280.00, and for hospitalization, the cost was $192,038.00; for the use of antimicrobials, an expense of $749,689.20 was calculated, and for the use of mechanical ventilation, the cost was $2,974,275.60. The percentage of decrease in the cost of VAP after CQIP implementation was 46.5%.

Conclusions

The implementation of CQIP based on the risk evaluation factors of VAP resulted in their decrease, which is reflected in a patient safety and quality care improvement.
Periorbital and Perioral Regions in Relation to Aging
Authors: Hwang Kun
Published: May 2020

The aim of this study was to determine the boundary between the periorbital and perioral regions based on a literature review.

PubMed was searched for the terms (zone [OR] area [OR] region) [AND] (face-lift [OR] rhytidectomy), and 872 abstracts were found. Additionally, the terms (levator labii superioris [AND] orbicularis oculi) resulted in 20 abstracts. The author separately searched for (Lightoller) because searching PubMed for terms in abstracts does not yield results for older papers that do not have abstracts.

Among the papers identified through this search strategy, the author did not find any that defined the boundary of the periorbital and perioral regions. However, the author found Lightoller's research on the subject and retrieved 8 articles that he authored. Two of his papers showed and described the origins of the facial muscles. Burkitt and Lightoller reported that the inferior bony origin of the pars orbitalis extended laterally to the medial end of the caput infraorbitale M. quadrati labii superioris. According to those authors, there was a definite boundary between the origins of the periorbital muscles (pars orbitalis and pars oculobuccalis of the orbicularis oculi) and the perioral muscles (caput infraorbitale of the quadratus labii superioris). Based on that article, it is possible to divide the face into periorbital and perioral regions based on the origin of the circumoral and circumocular muscles.

With this division, the surgical technique based on the concept of these 2 regions could be followed.
Prophylactic Use of the Pectoralis Major Flap to Prevent Anastomotic Leak in the Reconstruction of a Total Laryngopharyngoesophagectomy Defect Combined With Gastric Pull-Up After Chemoradiotherapy
Authors: Scott Britney , Harrison Lucas , Kadakia Sameep , Ducic Yadranko , Johnson R. Michael
Published: May 2020

Total laryngopharyngoesophagectomy defects after surgical ablation for laryngopharyngeal carcinoma with involvement of the cervical esophagus represents a challenge to the reconstructive surgeon. Complicating an already challenging operation is when surgical ablation occurs after failure of primary chemoradiation requiring the surgeon to operate and reconstruct in an irradiated field limiting potential reconstructive options. Due to the advanced stage at diagnosis, some studies have shown that while traditional management with radiotherapy may be considered as an initial treatment modality, often times this has failed to provide sustainable improvement in survival with reported high local recurrence rates. With relatively high local recurrence rates following radiotherapy, movement towards aggressive surgical resection is favored in some institutions. Despite this movement, primary treatment with chemoradiation is still commonly used as a primary modality opening up the opportunity for residual or recurrent disease leading the surgeon to perform salvage surgery to eradicate disease after primary treatment failure. With advanced ablative surgery comes the challenge to find an ideal reconstructive option that will optimize functional outcomes which has shown to be particularly challenging when operating in a post-radiated field with a higher risk for pharyngocutaneous fistulas. The authors present a case where reconstruction of such a defect after local failure with primary chemoradiation was successful using a single stage reconstruction with the gastric pull up technique in combination with a pectoralis major myocutaneous flap. As the risk of anastomotic leak is significantly higher in patients following radiation, this method showed utilizing a prophylactic muscle flap at the time of reconstruction may further bolster the repair and prevent anastomotic leak.
Best Practice Guidelines for the Management of Acute Craniomaxillofacial Trauma During the COVID-19 Pandemic
Authors: DeSerres Joshua J. , Al-Shaqsi Sultan Z. , Antonyshyn Oleh M. , Fialkov Jeffrey A.
Published: May 2020

Coronavirus disease 2019 (COVID-19) is an infectious disease that is caused by severe respiratory syndrome coronavirus 2. Although elective surgical procedures are being cancelled in many parts of the world during the COVID-19 pandemic, acute craniomaxillofacial (CMF) trauma will continue to occur and will need to be appropriately managed. Surgical procedures involving the nasal, oral, or pharyngeal mucosa carry a high risk of transmission due to aerosolization of the virus which is known to be in high concentration in these areas. Intraoperative exposure to high viral loads through aerosolization carries a very high risk of transmission, and the severity of the disease contracted in this manner is worse than that transmitted through regular community transmission. This places surgeons operating in the CMF region at particularly high risk during the pandemic. There is currently a paucity of information to delineate the best practice for the management of acute CMF trauma during the COVID-19 pandemic. In particular, a clear protocol describing optimal screening, timing of intervention and choice of personal protective equipment, is needed. The authors have proposed an algorithm for management of CMF trauma during the COVID-19 pandemic to ensure that urgent and emergent CMF injuries are addressed appropriately while optimizing the safety of surgeons and other healthcare providers. The algorithm is based on available evidence at the time of writing. As the COVID-19 pandemic continues to evolve and more evidence and better testing becomes available, the algorithm should be modified accordingly.
Safe Cholecystectomy Multi-society Practice Guideline and State of the Art Consensus Conference on Prevention of Bile Duct Injury During Cholecystectomy
Authors: Brunt L. Michael , Deziel Daniel J. , Telem Dana A. , Strasberg Steven M. , Aggarwal Rajesh , Asbun Horacio , Bonjer Jaap , McDonald Marian , Alseidi Adnan , Ujiki Mike , Riall Taylor S. , Hammill Chet , Moulton Carol-Anne , Pucher Philip H. , Parks Rowan W. , Ansari Mohammed T. , Connor Saxon , Dirks Rebecca C. , Anderson Blaire , Altieri Maria S. , Tsamalaidze Levan , Stefanidis Dimitrios
Published: May 2020

Background:

BDI is the most common serious complication of laparoscopic cholecystectomy. To address this problem, a multi-society consensus conference was held to develop evidenced-based recommendations for safe cholecystectomy and prevention of BDI.

Methods:

Literature reviews were conducted for 18 key questions across 6 broad topics around cholecystectomy directed by a steering group and subject experts from 5 surgical societies (Society of Gastrointestinal and Endoscopic Surgeons, Americas Hepato-Pancreato-Biliary Association, International Hepato-Pancreato-Biliary Association, Society for Surgery of the Alimentary Tract, and European Association for Endoscopic Surgery). Evidence-based recommendations were formulated using the grading of recommendations assessment, development, and evaluation methodology. When evidence-based recommendations could not be made, expert opinion was documented. A number of recommendations for future research were also documented. Recommendations were presented at a consensus meeting in October 2018 and were voted on by an international panel of 25 experts with greater than 80% agreement considered consensus.

Results:

Consensus was reached on 17 of 18 questions by the guideline development group and expert panel with high concordance from audience participation. Most recommendations were conditional due to low certainty of evidence. Strong recommendations were made for (1) use of intraoperative biliary imaging for uncertainty of anatomy or suspicion of biliary injury; and (2) referral of patients with confirmed or suspected BDI to an experienced surgeon/multispecialty hepatobiliary team.

Conclusions:

These consensus recommendations should provide guidance to surgeons, training programs, hospitals, and professional societies for strategies that have the potential to reduce BDIs and positively impact patient outcomes. Development of clinical and educational research initiatives based on these recommendations may drive further improvement in the quality of surgical care for patients undergoing cholecystectomy.
Personal Protective Equipment and COVID-19
Authors: Stewart Camille L. , Thornblade Lucas W. , Diamond Don J. , Fong Yuman , Melstrom Laleh G.
Published: May 2020

There is a long history of personal protective equipment (PPE) used by the surgeon to minimize the transmission of various pathogens. In the context of the present coronavirus disease 2019 pandemic there is significant controversy as to what forms of PPE are appropriate or adequate. This review aims to describe the pathogenic mechanism and route of spread of the causative virus, severe acute respiratory syndrome coronavirus, as it pertains to accumulated published data from experienced centers globally. The various forms of PPE that are both available and appropriate are addressed. There are options in the form of eyewear, gloves, masks, respirators, and gowns. The logical and practical utilization of these should be data driven and evolve based on both experience and data. Last, situations specific to surgical populations are addressed. We aim to provide granular collective data that has thus far been published and that can be used as a reference for optimal PPE choices in the perioperative setting for surgical teams.
The Work Organisation Assessment Questionnaire: validation for use with community nurses and paramedics
Authors: Karimi Leila , Oakman Jodi
Published: May 2020

Aim:

The current study aimed to assess the suitability of the Work Organisation Assessment Questionnaire (WOAQ) for use in the healthcare sector, specifically for community nurses and paramedics. Community nurses and paramedics work in complex environments and are exposed to a range of psychosocial hazards linked with the development of musculoskeletal and mental health disorders. To reduce the incidence of these disorders, assessment and then control of psychosocial hazards is required. WOAQ addresses this need through an employee survey to identify key hazards, with the responses used to underpin a participative development of solutions.

Method:

Using a bifactor model, the WOAQ and five nested factors were cross validated using a sample of 1255 community nurses and paramedics using data collected in 2011 and 2012.

Results:

The results of metric invariance testing demonstrated that the WOAQ is a valid tool across health organizations. Full invariance testing at mean constructs level also showed strong support of validity of the ‘general score’ of the WOAQ. However, minor mean differences were found between two nested factors (workload issues and the relationships with the coworkers).

Conclusion:

The WOAQ is a valid assessment tool for application within the nursing and paramedic settings. Practical implications for these findings in healthcare settings are discussed.
Teenage dogs? Evidence for adolescent-phase conflict behaviour and an association between attachment to humans and pubertal timing in the domestic dog
Authors: Asher Lucy , England Gary C. W. , Sommerville Rebecca , Harvey Naomi D.
Published: May 2020

The relationship between parent and child changes around adolescence, with children believed to have: (i) an earlier puberty if they have less secure attachments to their carer; (ii) a phase of increased conflict behaviour toward their carer; and (iii) heightened conflict behaviour when carer attachments are less secure. We find support for analogous associations in adolescent dogs based on behaviour and reproductive timing of potential guide dogs. Bitches with behaviour indicative of insecure attachments pre-adolescence became reproductively capable earlier. Providing the first empirical evidence to our knowledge in support of adolescent-phase behaviour in dogs, we found a passing phase of carer-specific conflict-like behaviour during adolescence (reduced trainability and responsiveness to commands), an effect that was more pronounced in dogs with behaviour indicative of less secure attachments. These results indicate a possibility for cross-species influence on reproductive development and highlight adolescence as a vulnerable time for dog–owner relationships.
The impacts of ocean acidification on marine trace gases and the implications for atmospheric chemistry and climate
Authors: Hopkins Frances E. , Suntharalingam Parvadha , Gehlen Marion , Andrews Oliver , Archer Stephen D. , Bopp Laurent , Buitenhuis Erik , Dadou Isabelle , Duce Robert , Goris Nadine , Jickells Tim , Johnson Martin , Keng Fiona , Law Cliff S. , Lee Kitack , Liss Peter S. , Lizotte Martine , Malin Gillian , Murrell J. Colin , Naik Hema , Rees Andrew P. , Schwinger Jörg , Williamson Philip
Published: May 2020

Surface ocean biogeochemistry and photochemistry regulate ocean–atmosphere fluxes of trace gases critical for Earth's atmospheric chemistry and climate. The oceanic processes governing these fluxes are often sensitive to the changes in ocean pH (orpCO2) accompanying ocean acidification (OA), with potential for future climate feedbacks. Here, we review current understanding (from observational, experimental and model studies) on the impact of OA on marine sources of key climate-active trace gases, including dimethyl sulfide (DMS), nitrous oxide (N2O), ammonia and halocarbons. We focus on DMS, for which available information is considerably greater than for other trace gases. We highlight OA-sensitive regions such as polar oceans and upwelling systems, and discuss the combined effect of multiple climate stressors (ocean warming and deoxygenation) on trace gas fluxes. To unravel the biological mechanisms responsible for trace gas production, and to detect adaptation, we propose combining process rate measurements of trace gases with longer term experiments using both model organisms in the laboratory and natural planktonic communities in the field. Future ocean observations of trace gases should be routinely accompanied by measurements of two components of the carbonate system to improve our understanding of howin situcarbonate chemistry influences trace gas production. Together, this will lead to improvements in current process model capabilities and more reliable predictions of future global marine trace gas fluxes.
Heterogeneity in evolutionary games: an analysis of the risk perception
Authors: Amaral Marco A. , Javarone Marco A.
Published: May 2020

In this study, we analyse the relationship between heterogeneity and cooperation. Previous investigations suggest that this relation is non-trivial, as some authors found that heterogeneity sustains cooperation, while others obtained different results. Among the possible forms of heterogeneity, we focus on the individual perception of risks and rewards related to a generic event, which can appear in a number of social and biological systems. The modelling approach is based on the framework of evolutionary game theory. To represent this kind of heterogeneity, we implement small and local perturbations on the pay-off matrix of simple two-strategy games, such as the Prisoner’s Dilemma. So, while usually the pay-off is considered to be a global and time-invariant structure, i.e. it is the same for all individuals of a population at any time, in our model its value is continuously affected by small variations, in both time and space (i.e. position on a lattice). We found that such perturbations can be beneficial or detrimental to cooperation, depending on their setting. Notably, cooperation is strongly supported when perturbations act on the main diagonal of the pay-off matrix, whereas when they act on the off-diagonal the resulting effect is more difficult to quantify. To conclude, the proposed model shows a rich spectrum of possible equilibria, whose interpretation might offer insights and enrich the description of several systems.
‘The last channel’: vision at the temporal margin of the field
Authors: Veto P. , Thomas P. B. M. , Alexander P. , Wemyss T. A. , Mollon J. D.
Published: May 2020

The human visual field, on the temporal side, extends to at least 90° from the line of sight. Using a two-alternative forced-choice procedure in which observers are asked to report the direction of motion of a Gabor patch, and taking precautions to exclude unconscious eye movements in the direction of the stimulus, we show that the limiting eccentricity of image-forming vision can be established with precision. There are large, but reliable, individual differences in the limiting eccentricity. The limiting eccentricity exhibits a dependence on log contrast; but it is not reduced when the modulation visible to the rods is attenuated, a result compatible with the histological evidence that the outermost part of the retina exhibits a high density of cones. Our working hypothesis is that only one type of neural channel is present in the far periphery of the retina, a channel that responds to temporally modulated stimuli of low spatial frequency and that is directionally selective.
Evidence of Protective Role of Ultraviolet-B (UVB) Radiation in Reducing COVID-19 Deaths Manuscript
Authors: Moozhipurath Rahul Kalippurayil , Kraft Lennart , Skiera Bernd
Published: May 2020

Background

Research is ongoing to identify an effective way to prevent or treat COVID-19, but thus far these efforts have not yet identified a possible solution. Prior studies indicate the protective role of Ultraviolet-B (UVB) radiation in human health, mediated by vitamin D synthesis. In this study, we empirically outline a negative association of UVB radiation as measured by ultraviolet index (UVI) with the number of deaths attributed to COVID-19 (COVID-19 deaths).

Methods

We carry out an observational study, applying a fixed-effect log-linear regression model to a panel dataset of 64 countries over a period of 78 days (n=4992). We use the cumulative number of COVID-19 deaths and case-fatality rate (CFR) as the main dependent variables to test our hypothesis and isolate UVI effect from potential confounding factors such as underlying time trends, country-specific time-constant and time-varying factors such as weather.

Findings

After controlling for time-constant and time-varying factors, we find that a permanent unit increase in UVI is associated with a 2.2 percentage points decline in daily growth rates of cumulative COVID-19 deaths [p < 0.01] as well as a 1.9 percentage points decline in the daily growth rates of CFR [p < 0.05]. These results represent a significant percentage reduction in terms of the daily growth rates of cumulative COVID-19 deaths (−22.92%) and CFR (−73.08%). Our results are consistent across different model specifications.

Interpretation

We find a significant negative association between UVI and COVID-19 deaths, indicating evidence of the protective role of UVB in mitigating COVID-19 deaths. If confirmed via clinical studies, then the possibility of mitigating COVID-19 deaths via sensible sunlight exposure or vitamin D intervention will be very attractive because it is cost-effective and widely available.
Analysis of heterozygous PRKN variants and copy number variations in Parkinson’s disease
Authors: Yu Eric , Rudakou Uladzislau , Krohn Lynne , Mufti Kheireddin , Ruskey Jennifer A. , Asayesh Farnaz , Estiar Mehrdad A. , Spiegelman Dan , Surface Matthew , Fahn Stanley , Waters Cheryl H. , Greenbaum Lior , Espay Alberto J. , Dauvilliers Yves , Dupré Nicolas , Rouleau Guy A. , Hassin-Baer Sharon , Fon Edward A. , Alcalay Roy N. , Gan-Or Ziv
Published: May 2020

Background

Biallelic PRKN mutation carriers with Parkinson’s disease (PD) typically have an earlier disease onset, slow disease progression and, often, different neuropathology compared to sporadic PD patients. However, the role of heterozygous PRKN variants in the risk of PD is controversial.

Objectives

We aimed to examine the association between heterozygous PRKN variants, including single nucleotide variants and copy-number variations, and PD.

Methods

We fully sequenced PRKN in 2,809 PD patients and 3,629 healthy controls, including 1,965 late onset (63.97±7.79 years, 63% men) and 553 early onset PD patients (43.33±6.59 years, 68% men). PRKN was sequenced using targeted next-generation sequencing with molecular inversion probes. Copy-number variations were identified using a combination of multiplex ligation-dependent probe amplification and ExomeDepth. To examine whether rare heterozygous single nucleotide variants and copy-number variations in PRKN are associated with PD risk and onset, we used optimized sequence kernel association tests and regression models.

Results

We did not find any associations between all types of PRKN variants and risk of PD. Pathogenic and likely-pathogenic heterozygous single nucleotide variants and copy-number variations were less common among PD patients (1.52%) than among controls (1.8%, false discovery rate-corrected p=0.55). No associations with age at onset and in stratified analyses were found.

Conclusions

Heterozygous single nucleotide variants and copy-number variations in PRKN are not associated with Parkinson’s disease. Molecular inversion probes allow for rapid and cost-effective detection of all types of PRKN variants, which may be useful for pre-trial screening and for clinical and basic science studies specifically targeting PRKN patients.
The relationship between glycaemia, cognitive function, structural brain outcomes and dementia: A Mendelian randomization study in the UK Biobank
Authors: Garfield Victoria , Farmaki Aliki-Eleni , Fatemifar Ghazaleh , Eastwood Sophie V. , Mathur Rohini , Rentsch Christopher T. , Denaxas Spiros , Bhaskaran Krishnan , Smeeth Liam , Chaturvedi Nish
Published: May 2020

Aims

To investigate the relationship between glycaemia and cognitive function, brain structure and incident dementia using bidirectional Mendelian randomisation (MR).

Methods

UK Biobank (n~500,000) individuals, aged 40-69 years at baseline. Our exposures were genetic instruments for type-2 diabetes (163 variants) and HbA1c (52 variants) and our outcomes were reaction time (RT - milliseconds), visual memory (number of incorrect responses), hippocampal and white matter hyperintensity volumes (both mm3), Alzheimer’s disease (AD). To study potential bidirectional effects, we then investigated the associations between genetic variants for RT (43 variants) and clinical type-2 diabetes and measured HbA1c. We used conventional inverse-variance weighted (IVW) MR, alongside standard MR sensitivity analyses.

Results

Using IVW, genetic liability to type-2 diabetes was not associated with reaction time (exponentiated ß=1.00, 95%CI=1.00; 1.00), visual memory (expß=1.00, 95%CI=0.99; 1.00), white matter hyperintensity volume (expß=0.98, 95%CI=0.93; 1.03), hippocampal volume (coefficient mm3=0.00, 95%CI=-0.01; 0.01) or risk of AD (OR 0.97, 95%CI=0.89; 1.06). HbA1c was not associated with reaction time (expß=1.01, 95%CI=1.00; 1.01), white matter hyperintensity volume (expß=0.88, 95%CI=0.73; 1.07), hippocampal volume (coefficient=-0.02, 95%CI=-0.10; 0.06), risk of AD (OR 0.94, 95%CI=0.47; 1.86), but HbA1c was associated with visual memory (expß=1.06, 95%CI=1.05; 1.07) using a weighted median approach. IVW showed no evidence that reaction time was associated with diabetes (OR 0.96, 95%CI=0.63; 1.46) or HbA1c (coefficient=-0.08, 95%CI=-0.57; 0.42). MR-Egger intercept p-values indicated no major issues with unbalanced horizontal pleiotropy (all p>0.05).

Conclusions

Overall, we observed little evidence of causal associations between glycaemia and cognition, structural brain and dementia phenotypes.

Abbreviations

Alzheimer’s dementia (AD)

Benjamini-Hochberg false discovery rate (BH-FDR)

Genome-wide association study (GWAS)

Hippocampal volume (HV)

Hospital episode statistics (HES)

International Classification of Diseases (ICD)

Inverse variance weighted (IVW)

Magnetic resonance imaging (MRI)

Mendelian randomization (MR)

Quality control (QC)

Reaction time (RT)

Simulation extrapolation (SIMEX)

UK Biobank (UKB)

Visual memory (VM)

Weighted median Estimator (WME)

White matter hyperintensity volume (WMHV)
Text Mining Approach to Analyze Coronavirus Impact: Mexico City as Case of Study
Authors: Saire Josimar Edinson Chire , Pineda Briseño Anabel
Published: May 2020

The epidemiological outbreak of a novel coronavirus (2019-nCoV or Covid-19) in China, and its rapid spread, gave rise to the first pandemic in the digital age. Derived from this fact that has surprised humanity, many countries started with different strategies in order to stop the infection. In this context, one of the greatest challenges for the scientific community is monitoring (real time) the global population to get immediate feedback of what is happening with the people during this public health contingency. An alternative interesting and affordable for the materialization of the aforementioned are the social networks. In a social network, the persons can act as sensors/information not only of personal data but also data derived from their behavior. This paper aims to analyze the publications of people in Mexico using a Text Mining approach. Specifically, Mexico City is presented as a case study to help understand the impact on society of the spread of Covid-19.
Early outcomes of tocilizumab in adults hospitalized with severe COVID-19 - The Vall d’Hebron COVID-19 prospective cohort study
Authors: Sánchez-Montalvá Adrián , Sellarés-Nadal Júlia , Espinosa-Pereiro Juan , Fernández-Hidalgo Nuria , Pérez-Hoyos Santiago , Salvador Fernando , Durà Xavier , Miarons Marta , Antón Andrés , Eremiev-Eremiev Simeón , Sempere-González Abiu , Monforte-Pallarés Arnau , Bosch-Nicolau Pau , Augustin Salvador , Sampol Júlia , Guillén-del-Castillo Alfredo , Almirante Benito
Published: May 2020

Background

Modulation of the immune system to prevent lung injury is being widely used against the new coronavirus disease (COVID-19) despite the scarcity of evidence.

Methods

We report the preliminary results from the Vall d’Hebron prospective cohort study at Vall d’Hebron University Hospital, in Barcelona (Spain), including all consecutive patients who had a confirmed infection with the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and who were treated with tocilizumab until March 25th. The primary endpoint was mortality at 7 days after tocilizumab administration. Secondary endpoints were admission to the intensive care unit, development of ARDS and respiratory insufficiency among others.

Results

82 patients with COVID-19 received at least one dose of tocilizumab. The mean (± SD) age was 59.1 (19.8) years, 63% were male, 22% were of non-Spanish ancestry, and the median (IQR) age-adjusted Charlson index at baseline was 3 (1-4) points. Respiratory failure and ARDS developed in 62 (75.6%) and 45 (54.9%) patients, respectively. Median time from symptom onset to ARDS development was 8 (5-11) days. The median time from symptom onset to the first dose of tocilizumab was 9 (7-11) days. Mortality at 7 days was 26.8%. Hazard ratio for mortality was 3.3; 95% CI, 1.3 to 8.5 (age-adjusted hazard ratio for mortality 2.1; 95% CI, 0.8 to 5.8) if tocilizumab was administered after the onset of ARDS.

Conclusion

Time from lung injury onset to tocilizumab administration may be critical to patient recovery. Our preliminary data could inform bedside decisions until more data from clinical trials becomes available.

Summary of the article’s main point

In patient with COVID-19 and lung injury, time from lung injury onset to tocilizumab administration may be critical to patient recovery. Early administration of host-directed therapies may improve patient outcome.
Silent dissemination of plasmid-borne tigecycline resistance genetet(X6) in livestock-associatedAcinetobacter towneri
Authors: Cheng Yingying , Chen Yong , Liu Yang , Song Jingjie , Guo Yuqi , Zhou Yanzi , Xiao Tingting , Zhang Shuntian , Xu Hao , Chen Yunbo , Shan Tongling , Xiao Yonghong , Zhou Kai
Published: May 2020

A tigecycline-resistance gene,tet(X6), was detected on a 159-kb novel plasmid carried by a tigecycline-susceptible livestock-associatedAcinetobacter towneriisolate. The genetic context oftet(X6) (ΔISVsa3-tet(X6)-abh-guaA-ISVsa3) is highly similar with that of the other plasmid-bornetet(X) variants. The 23-Ala residue of the first FAD binding site conferred higher activity to Tet(X6) than the 23-Gly reside conserved in the other plasmid-bornetet(X)s. To our knowledge, this is the first report oftet(X6) carried by the plasmid.
Pre-Procedural Surveillance Testing for SARS-CoV-2 in an Asymptomatic Population Shows Low Rates of Positivity
Authors: Mays James A , Greninger Alexander L , Jerome Keith R , Lynch John B , Mathias Patrick C
Published: May 2020

Background: Depression is a common cause of mortality and morbidity worldwide. To detect depression, we compared Beck Depression Inventory scoring as a valid tool with participants self-reporting depression.Methodology: This cross-sectional study aimed to explore the diagnostic values of self-reporting in patients' with depression comparing to Beck Depression Inventory scoring in Mazandaran Persian cohort study, with a total of 1300 samples. The sample size was determined to include 155 participants through the census method. In order to increase the test power, 310 healthy participants were included in the study through random selection. In order to evaluate the diagnostic value of self-reporting, BDI-II was completed by blind interviewing to the case group as well as to another group who reported that they were not depressed, as control.

Results: sensitivity, specificity, accuracy, false positive, false negative, positive and negative predictive values of self-reporting was calculated 58.4%, 79.1%,73.4%, 20.8%, 41.6%, 51.8%, and 83.2% for the total population respectively, as well as, sensitivity, specificity, accuracy, positive and negative predictive values of self-report in males were 83.3%, 77.2%, 77.1%, 43.8% and 95.6% and 53.7%, 78.1%, 71.2%, 49.2%, and 81.1% for females, respectively.

Conclusion: The positive predictive value and sensitivity of self-reporting are insufficient in total population and females, and therefore self-reporting cannot detect depressed patients, but regarding to its average positive predictive value, perhaps, it can be used to identify non-depressant individuals.
Correlation Between Blood and CSF Compartment Cytokines and Chemokines in Subjects with Cryptococcal Meningitis
Authors: Okafor Elizabeth C , Hullsiek Katherine H , Williams Darlisha A , Scriven James E , Rhein Joshua , Nabeta Henry W , Musubire Abdu K , Rajasingham Radha , Muzoora Conrad , Schutz Charlotte , Meintjes Graeme , Meya David B , Boulware David R
Published: May 2020

Background

Though peripheral blood is a crucial sample to study immunology, it is unclear whether the immune environment in the peripheral vasculature correlates with that at the endorgan site of infection. Utilizing cryptococcal meningitis as a model, we investigated the correlation between serum and cerebrospinal fluid biomarkers over time.

Methods

We analyzed the cerebrospinal fluid and serum of 160 subjects presenting with first episode cryptococcal meningitis for soluble cytokines and chemokines measured by Luminex assay. Specimens were collected at meningitis diagnosis, 1-week, and 2-weeks post cryptococcal diagnosis. We compared paired samples by Spearman correlation and the p-value was set at <0.01.

Results

Of the 21 analytes tested at baseline, there was no correlation detected between nearly all analytes. A weak negative correlation was found between serum and cerebrospinal fluid levels of interferon-gamma (Rho= −0.214, p= .007) and interleukin-4 (Rho= −0.232, p=. 003). There was no correlation at 1-week post cryptococcal diagnosis. However, at 2-weeks post diagnosis, there was a weak positive correlation between levels of granulocyte-macrophage colony-stimulating factor (Rho= 0.25, p= .007) between serum and cerebrospinal fluid. No cytokine or chemokine showed consistent correlation overtime.

Conclusion

Based on our analysis of 21 biomarkers, serum and cerebrospinal fluid immune responses do not correlate. There appears to be a distinct immune environment in terms of soluble biomarkers in the vasculature versus end-organ site of infection. While this is a model of HIV-related cryptococcal meningitis, we postulate that assuming the blood compartment is representative of the immune function at the end-organ site of infection may not be appropriate.
Total predicted MHC-I epitope load is inversely associated with population mortality from SARS-CoV-2
Authors: Wilson Eric A. , Hirneise Gabrielle , Singharoy Abhishek , Anderson Karen S.
Published: May 2020

Abstract

Polymorphisms in MHC-I protein sequences across human populations significantly impacts viral peptide binding capacity and thus alters T cell immunity to infection. Consequently, allelic variants of the MHC-I protein have been found to be associated with patient outcome to various viral infections, including SARS-CoV. In the present study, we assess the relationship between observed SARS-CoV-2 population mortality and the predicted viral binding capacities of 52 common MHC-I alleles. Potential SARS-CoV-2 MHC-I peptides were identified using a consensus MHC-I binding and presentation prediction algorithm, called EnsembleMHC. Starting with nearly 3.5 million candidates, we resolved a few hundred highly probable MHC-I peptides. By weighing individual MHC allele-specific SARS-CoV-2 binding capacity with population frequency in 23 countries, we discover a strong inverse correlation between the predicted population SARS-CoV-2 peptide binding capacity and observed mortality rate. Our computations reveal that peptides derived from the structural proteins of the virus produces a stronger association with observed mortality rate, highlighting the importance of S, N, M, E proteins in driving productive immune responses. The correlation between epitope binding capacity and population mortality risk remains robust across a range of socioeconomic and epidemiological factors. A combination of binding capacity, number of deaths due to COPD complications, gender demographics. and the proportions of the population that were over the age of 65 and overweight offered the strongest determinant of at-risk populations. These results bring to light how molecular changes in the MHC-I proteins may affect population-level outcomes of viral infection.
Genetic drift versus regional spreading dynamics of COVID-19
Authors: Pietro R. Di , Basile M. , Antolini L. , Alberti S.
Published: May 2020

Background

Current propagation models of COVID-19 are poorly consistent with existing epidemiological data and with evidence that the SARS-CoV-2 genome is mutating, for potential aggressive evolution of the disease.

Methods

We challenged regional versus genetic evolution models of COVID-19 at a whole-population level, over 168,089 laboratory-confirmed SARS-CoV-2 infection cases in Italy, Spain and Scandinavia. Diffusion data in Germany, France and UK provided a validation dataset of 210,239 additional cases.

Results

The mean doubling time of COVID-19 cases was 6.63 days in Northern versus 5.38 days in Southern Italy. Spain extended this trend of faster diffusion in Southern Europe, with a doubling time of 4.2 days. Slower doubling times were observed in Sweden (9.4 days), Finland (10.8 days), Norway (12.95 days). COVID-19 doubling time in Germany (7.0 days), France (7.5 days) and UK (7.2 days) supported the North/South gradient model. Clusters of SARS-CoV-2 mutations upon sequential diffusion across distinct geographic areas were not found to clearly correlate with regional distribution dynamics.

Conclusions

Acquisition of mutations, upon SARS-CoV-2 spreading across distinct geographic areas, did not distinctly associate to enhanced virus aggressiveness, and failed to explain regional diffusion heterogeneity at early phases of the pandemic. Our findings indicate that COVID-19 transmission rates associate to a sharp North/South climate gradient, with faster spreading in Southern regions. Thus, warmer climate conditions may not limit SARS-CoV-2 infectivity. Very cold regions may be better spared by recurrent courses of SARS-CoV-2 infection.
Historical population declines prompted significant genomic erosion in the northern and southern white rhinoceros (Ceratotherium simum)
Authors: Sánchez-Barreiro Fátima , Gopalakrishnan Shyam , Ramos-Madrigal Jazmín , Westbury Michael V. , de Manuel Marc , Margaryan Ashot , Ciucani Marta M. , Vieira Filipe G. , Patramanis Yannis , Kalthoff Daniela C. , Timmons Zena , Sicheritz-Pontén Thomas , Dalén Love , Ryder Oliver A. , Zhang Guojie , Marquès-Bonet Tomás , Moodley Yoshan , Gilbert M. Thomas P.
Published: May 2020

Large vertebrates are extremely sensitive to anthropogenic pressure, and their populations are declining fast. The white rhinoceros (Ceratotherium simum) is a paradigmatic case: this African megaherbivore suffered a remarkable population reduction in the last 150 years due to human activities. The two white rhinoceros subspecies, the northern (NWR) and the southern white rhinoceros (SWR), however, underwent opposite fates: the NWR vanished quickly after the onset of the decline, while the SWR recovered after a severe bottleneck. Such demographic events are predicted to have an erosive effect at the genomic level, in connection with the extirpation of diversity, and increased genetic drift and inbreeding. However there is currently little empirical data available that allows us to directly reconstruct the subtleties of such processes in light of distinct demographic histories. Therefore to assess these effects, we generated a whole-genome, temporal dataset consisting of 52 re-sequenced white rhinoceros genomes, that represents both subspecies at two time windows: before and during/after the bottleneck. Our data not only reveals previously unknown population substructure within both subspecies, but allowed us to quantify the genomic erosion undergone by both, with post-bottleneck white rhinoceroses harbouring significantly fewer heterozygous sites, and showing higher inbreeding coefficients than pre-bottleneck individuals. Moreover, the effective population size suffered a decrease of two and three orders of magnitude in the NWR and SWR respectively, due to the recent bottleneck. Our data therefore provides much needed empirical support for theoretical predictions about the genomic consequences of shrinking populations, information that is relevant for understanding the process of population extinction. Furthermore, our findings have the potential to inform management approaches for the conservation of the remaining white rhinoceroses.
Predicting tissue-specific gene expression from whole blood transcriptome
Authors: Basu Mahashweta , Wang Kun , Ruppin Eytan , Hannenhalli Sridhar
Published: May 2020

Complex diseases are systemic, largely mediated via transcriptional dysregulation in multiple tissues. Thus, knowledge of tissue-specific transcriptome in an individual can provide important information about an individual’s health. Unfortunately, with a few exceptions such as blood, skin, and muscle, an individual’s tissue-specific transcriptome is not accessible through non-invasive means. However, due to shared genetics and regulatory programs between tissues, the transcriptome in blood may be predictive of those in other tissues, at least to some extent. Here, based on GTEx data, we address this question in a rigorous, systematic manner, for the first time. We find that an individual’s whole blood gene expression and splicing profile can predict tissue-specific expression levels in a significant manner (beyond demographic variables) for many genes. On average, across 32 tissues, the expression of about 60% of the genes is predictable from blood expression in a significant manner, with a maximum of 81% of the genes for the musculoskeletal tissue. Remarkably, the tissue-specific expression inferred from the blood transcriptome is almost as good as the actual measured tissue expression in predicting disease state for six different complex disorders, including Hypertension and Type 2 diabetes, substantially surpassing predictors built directly from the blood transcriptome. The code for our pipeline for tissue-specific gene expression prediction – TEEBoT, is provided, enabling others to study its potential translational value in other indications.
SARS-CoV-2 ORF3b is a potent interferon antagonist whose activity is further increased by a naturally occurring elongation variant
Authors: Konno Yoriyuki , Kimura Izumi , Uriu Keiya , Fukushi Masaya , Irie Takashi , Koyanagi Yoshio , Nakagawa So , Sato Kei
Published: May 2020

One of the features distinguishing SARS-CoV-2 from its more pathogenic counterpart SARS-CoV is the presence of premature stop codons in itsORF3bgene. Here, we show that SARS-CoV-2ORF3bis a potent interferon antagonist, suppressing the induction of type I interferon more efficiently than its SARS-CoV ortholog. Phylogenetic analyses and functional assays revealed that SARS-CoV-2-related viruses from bats and pangolins also encode truncatedORF3bgene products with strong anti-interferon activity. Furthermore, analyses of more than 15,000 SARS-CoV-2 sequences identified a natural variant, in which a longerORF3breading frame was reconstituted. This variant was isolated from two patients with severe disease and further increased the ability of ORF3b to suppress interferon induction. Thus, our findings not only help to explain the poor interferon response in COVID-19 patients, but also describe a possibility of the emergence of natural SARS-CoV-2 quasispecies with extendedORF3bthat may exacerbate COVID-19 symptoms.

Highlights

ORF3b of SARS-CoV-2 and related bat and pangolin viruses is a potent IFN antagonist

SARS-CoV-2 ORF3b suppresses IFN induction more efficiently than SARS-CoV ortholog

The anti-IFN activity of ORF3b depends on the length of its C-terminus

An ORF3b with increased IFN antagonism was isolated from two severe COVID-19 cases
A Rapid, Cost-Effective Tailed Amplicon Method for Sequencing SARS-CoV-2
Authors: Gohl Daryl M. , Garbe John , Grady Patrick , Daniel Jerry , Watson Ray H. B. , Auch Benjamin , Nelson Andrew , Yohe Sophia , Beckman Kenneth B.
Published: May 2020

The global COVID-19 pandemic has led to an urgent need for scalable methods for clinical diagnostics and viral tracking. Next generation sequencing technologies have enabled large-scale genomic surveillance of SARS-CoV-2 as thousands of isolates are being sequenced around the world and deposited in public data repositories. A number of methods using both short- and long-read technologies are currently being applied for SARS-CoV-2 sequencing, including amplicon approaches, metagenomic methods, and sequence capture or enrichment methods. Given the small genome size, the ability to sequence SARS-CoV-2 at scale is limited by the cost and labor associated with making sequencing libraries. Here we describe a low-cost, streamlined, all amplicon-based method for sequencing SARS-CoV-2, which bypasses costly and time-consuming library preparation steps. We benchmark this tailed amplicon method against both the ARTIC amplicon protocol and sequence capture approaches and show that an optimized tailed amplicon approach achieves comparable amplicon balance, coverage metrics, and variant calls to the ARTIC v3 approach and represents a cost-effective and highly scalable method for SARS-CoV-2 sequencing.
Onion thrips Thrips tabaci [Thysanoptera: Thripidae] reduces yields and THC in indoor grown cannabis
Authors: McCune Frédéric , Murphy Chad , Eaves James , Fournier Valérie
Published: May 2020

Cannabis (Cannabis sativa L. [Rosales: Cannabaceae]) is a newly legalized crop and requires deeper insights on its pest communities. In this preliminary study, we identified a thrips species affecting indoor grown cannabis in Canada and tested its impact on plant yield. We used three levels of initial infestation (zero, one, and five thrips) on individual plants grown in two growing mediums: normal substrate or substrate containing the biostimulant Bacillus pumilus, Meyer and Gottheil [Bacillales: Bacillaceae]. We found that the onion thrips, Thrips tabaci (Lindeman) [Thysanoptera: Thripidae] is proliferating in indoor grown cannabis. Furthermore, our results showed that fresh yields were higher for the plants that initially received zero thrips compared to those that initially received five thrips. Moreover, the biostimulant did not help reduce the impact of thrips. We highlight the importance for growers to carefully monitor thrips infestations in indoor grown cannabis. Finally, we emphasize the need for more research related to the impact of pests on cannabis yields and safe means of pest control for this strictly regulated crop.
Twin-arginine translocase component TatB performs folding quality control via a general chaperone activity
Authors: Taw May N. , Boock Jason T. , Kim Daniel , Rocco Mark A. , Waraho-Zhmayev Dujduan , DeLisa Matthew P.
Published: May 2020

The twin-arginine translocation (Tat) pathway involves an inbuilt quality control (QC) system that synchronizes proofreading of substrate protein folding with lipid bilayer transport. However, the molecular details of this QC mechanism remain poorly understood. Here, we hypothesized that the conformational state of Tat substrates is directly sensed by the TatB component of the bacterial Tat translocase. In support of this hypothesis, several TatB variants in which the cytoplasmic membrane-extrinsic domain was either truncated or mutated in the vicinity of a conserved, highly flexible α-helical domain were observed to form functional translocasesin vivothat had compromised QC activity as evidenced by the uncharacteristic export of several misfolded protein substrates.In vitrofolding experiments revealed that the membrane-extrinsic domain of TatB possessed general chaperone activity, transiently binding to highly structured, partially unfolded intermediates of a model protein, citrate synthase, thereby preventing its irreversible aggregation and stabilizing the active species. Collectively, these results suggest that the Tat translocase may use chaperone-like client recognition to monitor the conformational status of its substrates.