bluuebunny/crossref_metadata_2025 huggingface dataset:
Prognostic risk factors of surgical site infection after primary joint arthroplasty
Authors: Yang Guang , Zhu Yanbin , Zhang Yingze
Published: February 2020

Surgical site infection (SSI) can be a devastating complication in joint arthroplasty. Objective of this study was to identify potential risk factors associated with SSI following primary joint arthroplasty.

This retrospective cohort study was performed from January 2016 to October 2017. A total of 986 patients were enrolled. We extracted the patients’ baseline information, treatment-related variables and indexes of laboratory examination during their hospitalization. Receiver operating characteristic (ROC) analysis was performed to find the optimum cut-off value for serum albumin. Univariate and multivariate logistic analysis models were performed respectively to determine independent predictors of SSI.

Nine hundred eighty-six patients with complete data were included in the final analysis. There were 314 male and 672 females in this study with a mean age of 64.6 years, and twenty patients developed SSI. The overall incidence of SSI was 2.03%, with 0.20% for deep infection and 1.83% for superficial SSI. Independent predictors of SSI identified by multivariate analysis were ALB < 36.7 g/L (odds ratio = 3.42; 95% CI = 1.24–9.48; P = .018), BMI ≥28 (odds ratio = 5.08; 95%CI = 1.52–17.01; P = .008) and ASA class 3 or higher (odds ratio = 3.36; 95% CI = 1.22–9.30; P = .019). Drain use was demonstrated as a protective factor of postoperative wound healing.

The incidence of SSI following primary joint arthroplasty was 2.03%. ASA ≥3, BMI ≥28 and ALB < 36.7 g/L were demonstrated as risk factors of postoperative wound infection. Supplementary nutrition support is necessary to reduce the risk of infection in patients who underwent artificial joint arthroplasty.
The adoption of electronic medical record by physicians
Authors: Dutta Bireswar , Hwang Hsin-Ginn
Published: February 2020

Background:

The electronic medical record (EMR) is considered to be a vital tool of information and communication technology (ICT) to improve the quality of medical care, but the limited adoption of EMR by physicians results in a considerable warning to its successful implementation. The purpose of the present review is to explore and identify the potential barriers perceived by physicians in the adoption of EMR.

Methods:

The systematic review was carried out based on literature published in 5 databases: PubMed, Web of Science, Scopus, The Cochrane Library, and ProQuest from 2014 to 2018, concerning barriers perceived by physicians to the adoption of EMR.

Results:

The present study incorporates 26 articles based on their appropriateness out of 1354 for the final analysis. Authors explore 25 barriers that appeared 112 times in the literature for the present review; the top 5 frequently mentioned barriers are privacy and security concerns, high start-up cost, workflow changes, system complexity, lack of reliability, and interoperability.

Conclusion:

The systematic review explores that physicians deal with different barriers as they intend to adopt EMR. The barriers explored in the present review are the potential to play as references for the implementer of the EMR system. Thus an attentive analysis of the definitive condition is needed before relevant intervention is determined as the implementation of EMR must be considered as a behavioral change in medical practice.
Association between neuropathic pain characteristics and DNA methylation of transient receptor potential ankyrin 1 in human peripheral blood
Authors: Takenaka Shiho , Sukenaga Norihiko , Ohmuraya Masaki , Matsuki Yuka , Maeda Lynn , Takao Yumiko , Hirose Munetaka
Published: February 2020

Elucidation of epigenetic mechanisms correlating with neuropathic pain in humans is crucial for the prevention and treatment of this treatment-resistant pain state. In the present study, associations between neuropathic pain characteristics and DNA methylation of the transient receptor potential ankyrin 1 (TRPA1) gene were evaluated in chronic pain patients and preoperative patients. Pain and psychological states were prospectively assessed in patients who suffered chronic pain or were scheduled for thoracic surgery. Neuropathic characteristics were assessed using the Douleur Neuropathique 4 (DN4) questionnaire. DNA methylation levels of the CpG islands in the TRPA1 gene were examined using whole blood. Forty-eight adult patients were enrolled in this study. Increases in DNA methylation rates at CpG -51 showed positive correlations with increases in the DN4 score both in preoperative and chronic pain patients. Combined methylation rates at CpG -51 in these patients also significantly increased together with increase in DN4 scores. Neuropathic pain characteristics are likely associated with methylation rates at the promoter region of the TRPA1 gene in human peripheral blood.
Clinical and Practice Variations in Pediatric Acute Recurrent or Chronic Pancreatitis
Authors: Dike Chinenye R. , Zimmerman Bridget , Zheng Yuhua , Wilschanski Michael , Werlin Steven L. , Troendle David , Shah Uzma , Schwarzenberg Sarah Jane , Pohl John , Perito Emily R. , Ooi Chee Y. , Nathan Jaimie D. , Morinville Veronique D. , McFerron Brian , Mascarenhas Maria , Maqbool Asim , Liu Quin , Lin Tom K. , Husain Sohail Z. , Heyman Melvin B. , Gonska Tanja , Giefer Matthew J. , Gariepy Cheryl E. , Fishman Douglas S. , Bellin Melena , Barth Bradley , Abu‐El‐Haija Maisam , Lowe Mark E. , Uc Aliye
Published: February 2020

Objective:

The aim of the study was to determine whether clinical characteristics and management of pediatric acute recurrent pancreatitis (ARP) and chronic pancreatitis (CP) differ across INSPPIRE (INternational Study Group of Pediatric Pancreatitis: In Search for a cuRE) sites.

Study Design:

Data were collected from INSPPIRE and analyzed per US regions and “non‐US” sites. Between‐group differences were compared by Pearson chi‐square test. Differences in disease burden were compared by Kruskal‐Wallis test.

Results:

Out of the 479 subjects, 121 (25%) were enrolled in West, 151 (32%) Midwest, 45 Northeast (9%), 78 (16%) South, and 84 (18%) at non‐US sites. Hispanic ethnicity was more common in South (P < 0.0001); white race in Northeast (P = 0.009). CP was less common and time from diagnosis of first acute pancreatitis to CP was longer in children at non‐US sites (P = 0.0002 and P = 0.011, respectively). Genetic mutations were most common among all groups; PRSS1 variants predominated in Midwest (P = 0.002). Gallstones were more frequent in South (P = 0.002). Endoscopic retrograde cholangiopancreatography (ERCP) and computed tomography (CT) imaging were more commonly utilized in United States compared with non‐United States (P < 0.0001), but there were no differences in the use of MRI/MRCP. Disease burden was highest in the West and Midwest, possibly as total pancreatectomy and islet autotransplantation (TPIAT) referral sites were located in these regions. All therapies were less commonly administered in non‐US sites (P < 0.0001).

Conclusions:

This is the first study to describe geographical variations in the INSPPIRE cohort, which possibly reflect variations in practice and referral patterns. The underlying reason behind the lower frequency of CP and fewer treatments in non‐United States sites need to be further explored.
The Roles of Endoscopic Ultrasound and Endoscopic Retrograde Cholangiopancreatography in the Evaluation and Treatment of Chronic Pancreatitis in Children
Authors: Liu Quin Y. , Gugig Roberto , Troendle David M. , Bitton Samuel , Patel Nishant , Vitale David S. , Abu‐El‐Haija Maisam , Husain Sohail Z. , Morinville Veronique D.
Published: February 2020

Introduction:

Pediatric chronic pancreatitis is increasingly diagnosed. Endoscopic methods [endoscopic ultrasound (EUS), endoscopic retrograde cholangiopancreatography (ERCP)] are useful tools to diagnose and manage chronic pancreatitis. Pediatric knowledge and use of these modalities is limited and warrants dissemination.

Methods:

Literature review of publications relating to use of ERCP and EUS for diagnosis and/or management of chronic pancreatitis with special attention to studies involving 0‐‐18 years old subjects was conducted with summaries generated. Recommendations were developed and voted upon by authors.

Results:

Both EUS and ERCP can be used even in small children to assist in diagnosis of chronic pancreatitis in cases where cross‐sectional imaging is not sufficient to diagnose or characterize the disease. Children under 15 kg for EUS and 10 kg for ERCP can be technically challenging. These procedures should be done optimally by appropriately trained endoscopists and adult gastroenterology providers with appropriate experience treating children. EUS and ERCP‐related risks both include perforation, bleeding and pancreatitis. EUS is the preferred diagnostic modality over ERCP because of lower complication rates overall. Both modalities can be used for management of chronic pancreatitis ‐related fluid collections. ERCP has successfully been used to manage pancreatic duct stones.

Conclusion:

EUS and ERCP can be safely used to diagnose chronic pancreatitis in pediatric patients and assist in management of chronic pancreatitis‐related complications. Procedure‐related risks are similar to those seen in adults, with EUS having a safer risk profile overall. The recent increase in pediatric‐trained specialists will improve access of these modalities for children.
Relative Accuracy of Bioelectrical Impedance Analysis for Assessing Body Composition in Children With Severe Obesity
Authors: Khan Soofia , Xanthakos Stavra A. , Hornung Lindsey , Arce‐Clachar Catalina , Siegel Robert , Kalkwarf Heidi J.
Published: February 2020

Objectives:

The accuracy of different bioelectrical impedance analysis (BIA) devices for assessing body composition in children with obesity is unclear. We determined the relative accuracy of 2 BIA devices compared to dual x‐ray absorptiometry (DXA) in obese and severely obese children.

Methods:

We measured body composition in a cross‐sectional study of 78 obese children by a handheld single frequency tetrapolar BIA device (Omron), a stationary multifrequency octopolar BIA device (InBody 370) and DXA. Intermethod agreement was assessed by intraclass correlations, paired t tests, and Bland‐Altman analyses.

Results:

Participants (37% female, age 14.8 ± 2.7 years) had mean (±standard deviation) body mass index of 36.7 ± 7.5 kg/m2, body fat percentage of 46.4% ± 5.2%, and appendicular lean mass of 22.5 ± 6.0 kg by DXA. Intraclass correlations with DXA for body fat percentage were 0.39 and 0.87 for single frequency tetrapolar and multifrequency octopolar BIA devices, respectively. The single frequency tetrapolar BIA underestimated body fat percentage by 5.5% ± 2.9% (P < 0.0001). Differences between the multifrequency octopolar BIA and DXA for body fat percentage (−1.1% ± 2.8%) and appendicular lean mass (−0.3 ± 1.4 kg) were small, and 95% limits of agreement were approximately ±5%.

Conclusions:

BIA machines vary in relative accuracy in measuring body composition in children who are obese and severely obese. The multifrequency octopolar BIA device accurately estimated body fat percentage and appendicular lean mass relative to DXA and has the advantage of point of care performance.
Acute Gastroenteritis in Children of the World
Authors: Guarino Alfredo , Aguilar Juliet , Berkley James , Broekaert Ilse , Vazquez‐Frias Rodrigo , Holtz Lori , Lo Vecchio Andrea , Meskini Toufik , Moore Sean , Rivera Medina Juan F. , Sandhu Bhupinder , Smarrazzo Andrea , Szajewska Hania , Treepongkaruna Suporn
Published: February 2020

The incidence of gastroenteritis has greatly reduced due to improved hygiene conditions in developing countries and the use of rotavirus vaccine. Still thousands of children, however, die from gastroenteritis, most of them in poor countries. Yet gastroenteritis management is simple, inexpensive, and effective and is largely the same all over the world. Universal guidelines for gastroenteritis guide the management and include simple interventions put forward early in the course of the disease. Treatment includes rehydration, continuing oral feeding, and anti‐infective drugs in selected clinical conditions related to the symptoms or to host‐related risk, and possible additional drug treatment to reduce the duration and severity of symptoms. There may be minor geographical differences in the treatment applied due to health care organizations that do not substantially change the standard universal recommendations. Prevention is recommended with sanitation interventions and rotavirus universal immunization. Implementation of those interventions through educational initiatives and local programs in target areas are needed. A series of recommendations for interventions, education, and research priorities are included here with the aim of reducing the burden of gastroenteritis, to be pursued by scientists, physicians, policy makers, and stakeholders involved. They include the need of recommendations for the management of gastroenteritis in malnourished children, in those with chronic conditions, in neonates, and in emergency settings. A reference system to score dehydration, the definition of optimal composition of rehydration solution and the indications for anti‐infective therapy are also included. Rotavirus immunization should be actively promoted, and evidence‐based guidelines should be universally implemented. Research priorities are also indicated.
Role of Metastatic Site Irradiation in Pediatric Patients With Metastatic Ewing Sarcoma
Authors: Grewal Amardeep S. , Li Yimei , Grewal Sharonjit K. , Bagatell Rochelle , Balamuth Naomi , Womer Richard , Kurtz Goldie , Tochner Zelig , Hill-Kayser Christine E.
Published: February 2020

Background:

The use of radiation therapy to treat metastases in patients with metastatic Ewing sarcoma (MES) has been controversial and variable. The authors report outcomes and patterns of failure after metastatic site irradiation (MSI).

Procedure:

A total of 27 pediatric patients with MES were treated with chemotherapy and received radiation therapy to their primary site. Ten patients additionally received MSI, which consisted of whole-lung irradiation (WLI) in patients with lung metastases. Metastatic sites were followed from diagnosis to the first relapse.

Results:

Median follow-up was 29 months. Seventy-eight percent of patients relapsed. Two-year progression-free survival (PFS) and overall survival with and without MSI were 30 versus 29% (log rank P=0.38) and 60 versus 70% (log rank P=0.11), respectively. The median time to relapse among patients who relapsed was 19.5 versus 12.3 months for those receiving MSI versus those who did not (P=0.04).

Seven of 20 (35%) patients with lung metastases received WLI±other MSI. Two-year PFS with and without MSI was 43% versus 23% (log rank P=0.02). Among patients with a complete response to computed tomography, 5 of 14 (36%) patients received MSI. Two-year PFS with and without MSI was 60% versus 33% (log rank P=0.04).

In the cohort of patients who relapsed, among all metastatic sites at diagnosis, the disease recurred at 15% of irradiated sites and 31% of unirradiated sites. On logistic regression, no factors were statistically associated with increased risk of recurrence at initial sites of metastases.

Conclusions:

Relapses frequently occur at sites of prior unirradiated disease in patients with MES. WLI may improve 2-year PFS, regardless of chemotherapy response. Further investigation of the role of MSI is warranted.
Decreased vancomycin susceptibility among Staphylococcus aureus clinical isolates and postulated platforms to explore rational drugs
Authors: Al-Marzoqi Ali H. , Kareem Sawsan M. , Alhuchaimi Sundus , Kadhim Hindi Nada K. , Ghasemian Abdolmajid
Published: February 2020

Vancomycin is among last-resort drugs for the elimination of serious methicillin-resistant Staphylococcus aureus (MRSA) infections. Suboptimal or prolonged exposure to vancomycin is a major cause of decreased vancomycin susceptibility being a great concern toward the eradication of related infections. This arises from genetic and metabolic alterations leading to cell wall thickness and mitigation of autolysis. Therefore, the study on the major mechanisms contributing to the development of heterogeneous vancomycin-intermediate S. aureus (hVISA) and VISA strains and development of novel and efficient therapeutic approaches is essential. This nonsusceptibility imposes a fitness burden on bacterial cells through adaptive changes not verified entirely. Cell wall thickening and expression of various cell wall-related enzymes are major mechanisms with this regard. Metabolic changes permit growth of VISA in the presence of vancomycin. Prolonged vancomycin consumption, previous MRSA colonization, hemodialysis dependence, residence in an ICU and use of indwelling devices account for major risk factors for VISA emergence, hence care should be taken to hinder their development. Inhibitors of amino sugar and purine biosynthesis have exhibited synergistic properties to kill VISA, postulating the efficiency of combination therapies. In addition, combination of vancomycin with each of metabolic inhibitors, β-lactams (mostly such as fosfomycin, cefazolin, cefepime, ceftaroline, nafcillin, meropenem and piperacillin-tazobactam) have been effective against VISA and hVISA. Combination therapy of MRSA and hVISA with vancomycin and non-β-lactams has exerted lower effects compared to β-lactams combination therapies.
Staff Working Life and Older Persons' Satisfaction With Care
Authors: Engström Maria , Högberg Hans , Strömberg Annika , Hagerman Heidi , Skytt Bernice
Published: February 2020

Background:

The importance of staff working life for staff well-being has been demonstrated in several studies; less research has focused on staff working life and older persons' satisfaction with care.

Purpose:

The study aim was to study relationships between 1) staff assessments of their structural conditions/empowerment in elderly care, psychological empowerment, and job satisfaction and (2) older persons' satisfaction with care.

Methods:

A multilevel, cross-sectional, and correlational design was applied using questionnaire data on working life (1021 staff members) and unit-level data (40 elderly care units) on older persons' satisfaction with care.

Results:

Statistically significant relationships were found between all 3 working life variables and older persons' satisfaction with care. Furthermore, the results revealed an indirect/mediating effect of job satisfaction between structural empowerment and satisfaction with care, but not for psychological empowerment.

Conclusions:

Staff structural empowerment, psychological empowerment, and job satisfaction are linked to older persons' satisfaction with care.
Application of Behavioral Risk Factor Surveillance System Sampling Weights to Transgender Health Measurement
Authors: Cicero Ethan C. , Reisner Sari L. , Merwin Elizabeth I. , Humphreys Janice C. , Silva Susan G.
Published: February 2020

Background

Obtaining representative data from the transgender population is fundamental to improving their health and well-being and advancing transgender health research. The addition of the Behavioral Risk Factor Surveillance System (BRFSS) gender identity measure is a promising step toward better understanding transgender health. However, methodological concerns have emerged regarding the validity of data collected from transgender participants and its effect on the accuracy of population parameters derived from those data.

Objectives

The aim of the study was to provide rationale substantiating concerns with the formulation and application of the 2015 BRFSS sampling weights and address the methodological challenges that arise when using this surveillance data to study transgender population health.

Methods

We examined the 2015 BRFSS methodology and used the BRFSS data to present a comparison of poor health status using two methodological approaches (a matched-subject design and the full BRFSS sample with sampling weights applied) to compare their effects on parameter estimates.

Results

Measurement error engendered by BRFSS data collection procedures introduced sex/gender identity discordance and contributed to problematic sampling weights. The sex-specific “raking” algorithm used by BRFSS to calculate the sampling weights was contingent on the classification accuracy of transgender by participants. Because of the sex/gender identity discordance of 74% of the transgender women and 66% of transgender men, sampling weights may not be able to adequately remove bias. The application of sampling weights has the potential to result in inaccurate parameter estimates when evaluating factors that may influence transgender health.

Discussion

Generalizations made from the weighted analysis may obscure the need for healthcare policy and clinical interventions aimed to promote health and prevent illness for transgender adults. Methods of public health surveillance and population surveys should be reviewed to help reduce systematic bias and increase the validity of data collected from transgender people.
Standardized Protocol Is Associated With a Decrease in Continuous Albuterol Use and Length of Stay in Critical Status Asthmaticus*
Authors: Melendez Elliot , Dwyer Danielle , Donelly Daria , Currier Denise , Nachreiner Daniel , Miller D. Marlowe , Hurlbut Julie , Pepin Michael J. , Agus Michael S. D. , Wong Jackson
Published: February 2020

Objectives:

The primary aim of this study was to reduce duration of continuous albuterol and hospital length of stay in critically ill children with severe status asthmaticus.

Design:

Observational prospective study from September 2012 to May 2016.

Setting:

Medicine ICU and intermediate care unit.

Patients:

Children greater than 2 years old with admission diagnosis of status asthmaticus admitted on continuous albuterol and managed via a standardized protocol.

Interventions:

The protocol was an iterative algorithm for escalation and weaning of therapy. The algorithm underwent three revisions. Iteration 1 concentrated on reducing duration on continuous albuterol; iteration 2 concentrated on reducing hospital length of stay; and iteration 3 concentrated on reducing helium-oxygen delivered continuous albuterol. Balancing measures included adverse events and readmissions.

Measurements and Results:

Three-hundred eighty-five patients were treated as follows: 123, 138, and 124 in iterations 1, 2, and 3, respectively. Baseline data was gathered from an additional 150 patients prior to protocol implementation. There was no difference in median age (6 vs 8 vs 7 vs 7 yr; p = 0.130), asthma severity score (9 vs 9 vs 9 vs 9; p = 0.073), or female gender (42% vs 41% vs 43% vs 48%; p = 0.757). Using statistical process control charts, the mean duration on continuous albuterol decreased from 24.9 to 17.5 hours and the mean hospital length of stay decreased from 76 to 49 hours. There was no difference in adverse events (0% vs 1% vs 4% vs 0%; p = 0.054) nor in readmissions (0% vs 0% vs 1% vs 2%; p = 0.254).

Conclusions:

Implementation of a quality improvement protocol in critically ill patients with status asthmaticus was associated with a decrease in continuous albuterol duration and hospital length of stay.
Improving Disposition Decision-Making for Pediatric Diabetic Ketoacidosis: A Quality Improvement Study
Authors: Kaushal Tara , Lord Katherine , Olsen Robert , Mehta Sanjiv , Clark Stephanie , Laskin Benjamin , Traynor Danielle , Taylor April , Shaw Kathy N. , Srinivasan Vijay
Published: February 2020

Introduction:

In many centers, children with diabetic ketoacidosis (DKA) receive care either in an endocrinology ward or a pediatric intensive care unit (PICU). We conducted a quality improvement (QI) initiative to reduce potentially avoidable PICU admissions of children with DKA without increasing endocrinology ward-to-PICU transfers.

Methods:

A survey of providers demonstrated opportunities to increase awareness of institutional criteria for PICU admissions of children with DKA. We created an electronic health record (EHR) dot-phrase, prepopulated with these criteria, and placed a note in the EHR for all patients with DKA as a reference for all providers. An EHR-based data report was created to monitor the disposition of DKA patients and the use of the dot-phrase (process measure). The primary outcome measure was the potentially avoidable PICU admissions for patients with DKA. Endocrinology ward-to-PICU transfers were tracked as a balancing measure to ensure safe disposition.

Results:

After the implementation of the dot-phrase, use was variable, but averaged 33.4% over 1 year. The percentage of DKA admissions classified as potentially avoidable PICU stays decreased from 4.1% to 0.5%, with a concurrent decrease in the total percentage of PICU admissions for DKA from 19.1% to 8.4%. The percentage of endocrinology ward-to-PICU transfers also declined from 0.8% to 0%.

Conclusions:

A novel EHR-based intervention increasing awareness and documentation of established pediatric DKA management guidelines can be used to safely reduce PICU admissions for DKA without increasing the rate of endocrinology ward-to-intensive care unit transfers.
A Review of Adverse Event Reports From Emergency Departments in the Veterans Health Administration
Authors: Gill Sonia , Mills Peter D. , Watts Bradley V. , Paull Douglas E. , Tomolo Anne
Published: February 2020

Background

Previous work assessing the frequency of adverse events in emergency medicine has been limited. The emergency department (ED) provides an initial point of care for millions of patients. Given the volume of patient encounters and the complexity of medical conditions treated in the ED, it is necessary to determine the system-based issues and associated contributing factors impacting patient safety.

Objectives

The aim of this retrospective study were to use root cause analysis reports of adverse events occurring in Veterans Health Administration EDs to understand the range of events that were happening and to determine the primary causes of these events as well as actions to prevent them.

Methods

Retrospective safety reports from EDs from Veterans Health Administration medical centers across the nation for a 2-year period (2015–2016) were coded by event type, root cause, and recommended actions.

Results

One hundred forty-four cases were included for analysis. The most common adverse events were as follows: delays in care (n = 38, 26.4%), elopements (n = 21, 14.6%), suicide attempts and deaths by suicide (n = 15, 10.4%), inappropriate discharges (n = 15, 10.4%), and errors in following procedures (n = 14, 9.7%). Overall, the most common root cause categories leading to adverse events were knowledge/educational deficits (11.4%), policies/procedures needing improvement (11.1%), and lack of standardized policies/procedures (9.4%).

Discussion

Root cause analysis reports are a useful tool to determine the primary systems-based factors of common adverse events in the ED. Recommendations made in this article for addressing these root causes and potentially ameliorating these events will be useful to EDs and related health systems.
Can Routinely Collected, Patient-Reported Wellness Predict National Early Warning Scores? A Multilevel Modeling Approach
Authors: Albutt Abigail , O’Hara Jane , Conner Mark , Lawton Rebecca
Published: February 2020

Objective

Measures exist to improve early recognition of and response to deteriorating patients in hospital. However, management of critical illness remains a problem globally; in the United Kingdom, 7% of the deaths reported to National Reporting and Learning System from acute hospitals in 2015 related to failure to recognize or respond to deterioration. The current study explored whether routinely recording patient-reported wellness is associated with objective measures of physiology to support early recognition of hospitalized deteriorating patients.

Methods

A prospective observation study design was used. Nurses on four inpatient wards were invited to participate and record patient-reported wellness during every routine observation (where possible) using an electronic observation system. Linear multilevel modeling was used to examine the relationship between patient-reported wellness, and national early warning scores (NEWS), and whether patient-reported wellness predicted subsequent NEWS.

Results

A significant positive relationship was found between patient-reported wellness and NEWS recorded at the next observation while controlling for baseline NEWS (β = 0.180, P = 0.033). A significant positive relationship between patient-reported wellness and NEWS (β = 0.229, P = 0.005) recorded during an observation 24 hours later while controlling for baseline NEWS was also found. Patient-reported wellness added to the predictive model for subsequent NEWS.

Conclusions

The preliminary findings suggest that patient-reported wellness may predict subsequent improvement or decline in their condition as indicated by objective measurements of physiology (NEWS). Routinely recording patient-reported wellness during observation shows promise for supporting the early recognition of clinical deterioration in practice, although confirmation in larger-scale studies is required.
X-ray Structure of Main Protease of the Novel Coronavirus SARS-CoV-2 Enables Design of α-Ketoamide Inhibitors
Authors: Zhang Linlin , Lin Daizong , Sun Xinyuanyuan , Rox Katharina , Hilgenfeld Rolf
Published: February 2020

A novel coronavirus has been identified as the causative agent of a massive outbreak of atypical pneumonia originating at Wuhan, Hubei province, China. Involved in the formation of the coronavirus replication complex, the viral main protease (Mpro, also called 3CLpro) represents an attractive target for therapy. We determined the crystal structure of the unliganded Mproat 1.75 Å resolution and used this structure to guide optimization of a series of alpha-ketoamide inhibitors. The main goal of the optimization efforts was improvement of the pharmacokinetic properties of the compounds. We further describe 1.95- and 2.20-Å crystal structures of the complex between the enzyme and the most potent alpha-ketoamide optimized this way. These structures will form the basis for further development of these compounds to antiviral drugs.
Voting-based integration algorithm improves causal network learning from interventional and observational data: an application to cell signaling network inference
Authors: Sinha Meghamala , Tadepalli Prasad , Ramsey Stephen A.
Published: February 2020

In order to increase statistical power for learning a causal network, data are often pooled from multiple observational and interventional experiments. However, if the direct effects of interventions are uncertain, multi-experiment data pooling can result in false causal discoveries. We present a new method, “Learn and Vote,” for inferring causal interactions from multi-experiment datasets. In our method, experiment-specific networks are learned from the data and then combined by weighted averaging to construct a consensus network. Through empirical studies on synthetic and real-world datasets, we found that for most of the larger-sized network datasets that we analyzed, our method is more accurate than state-of-the-art network inference approaches.
Crystal structure of the 2019-nCoV spike receptor-binding domain bound with the ACE2 receptor
Authors: Lan Jun , Ge Jiwan , Yu Jinfang , Shan Sisi , Zhou Huan , Fan Shilong , Zhang Qi , Shi Xuanling , Wang Qisheng , Zhang Linqi , Wang Xinquan
Published: February 2020

A novel and highly pathogenic coronavirus (2019-nCoV) has caused an outbreak in Wuhan city, Hubei province of China since December 2019, and soon spread nationwide and spilled over to other countries around the world. To better understand the initial step of infection at atomic-level, we determined the crystal structure of the 2019-nCoV spike receptor-binding domain (RBD) bound with the cell receptor ACE2 at 2.45 Å resolution. The overall ACE2-binding mode of the 2019-nCoV RBD is nearly identical to that of the SARS-CoV RBD, which also utilizes ACE2 as the cell receptor. Structural analysis identified residues in 2019-nCoV RBD critical for ACE2 binding, and majority of which are either highly conserved or shared similar side chain properties with those in the SARS-CoV RBD. Such similarity in structure and sequence strongly argue for a convergent evolution between 2019-nCoV and SARS-CoV RBD for improved binding to ACE2 despite of being segregated in different genetic lineages in the betacoronavirus genus. The epitopes of two SARS-CoV antibodies targeting the RBD are also analyzed with the 2019-nCoV RBD, providing insights into future identification of cross-reactive antibodies.
The expression of hemagglutinin by a recombinant Newcastle disease virus causes structural changes and alters innate immune sensing
Authors: Fiona Ingrao , Victoria Duchatel , Isabel Fernandez Rodil , Mieke Steensels , Eveline Verleysen , Jan Mast , Bénédicte Lambrecht
Published: February 2020

Recombinant Newcastle disease viruses (rNDV) have been used as bivalent vectors for vaccination against multiple economically important avian pathogens. NDV-vectored vaccines expressing the immunogenic H5 hemagglutinin (rNDV-H5) are considered attractive candidates to protect poultry from both highly pathogenic avian influenza (HPAI) and Newcastle disease (ND). However, the impact of the insertion of a recombinant protein, such as H5, on the biological characteristics of the parental NDV strain has been little investigated to date. The present study compared a rNDV-H5 vaccine and its parental NDV LaSota strain in terms of their structural and functional characteristics, as well as their recognition by the innate immune sensors. Structural analysis of the rNDV-H5 demonstrated a decreased number of fusion (F) and a higher number of hemagglutinin-neuraminidase (HN) glycoproteins compared to NDV LaSota. These structural differences were accompanied by increased hemagglutinating and neuraminidase activities of rNDV-H5. Duringin vitrorNDV-H5 infection, increased mRNA expression of TLR3, TLR7, MDA5, and LGP2 was observed, suggesting that the recombinant virus is recognized differently by sensors of innate immunity when compared with the parental NDV LaSota. Given the growing interest in using NDV as a vector against human and animal diseases, these data highlight the importance to thoroughly understand the recombinant vaccines structural organization, functional characteristics, and the immune responses elicited.
Interactive machine learning for fast and robust cell profiling
Authors: Laux Lisa , Cutiongco Marie F.A. , Gadegaard Nikolaj , Jensen Bjørn Sand
Published: February 2020

Automatic profiling of cell morphology is a powerful tool for inferring cell function. However, this technique retains a high barrier to entry. In particular, configuring image processing parameters for optimal cell profiling is susceptible to cognitive biases and dependent on user experience. Here, we use interactive machine learning to identify the optimum cell profiling configuration that maximises quality of the cell profiling outcome. The process is guided by the user, from whom a rating of the quality of a cell profiling configuration is obtained. We use Bayesian optimisation, an established machine learning algorithm, to learn from this information and automatically recommend the next configuration to examine with the aim to maximize the quality of the processing or analysis. Compared to existing interactive machine learning tools that require domain expertise for per-class or per-pixel annotations, we rely on users explicit assessment of output quality of the cell profiling task at hand. We validated our interactive approach against the standard human trial-and-error scheme to optimise an object segmentation task using the standard software CellProfiler. Our toolkit enabled rapid optimisation of an object segmentation pipeline, increasing the quality of object segmentation over a pipeline optimised through trial-and-error. Users also attested to the ease of use and reduced cognitive load enabled by our machine learning strategy over the standard approach. We envision that our interactive machine learning approach can enhance the quality and efficiency of pipeline optimisation to democratise image-based cell profiling.
Hierarchical dinucleotide distribution in genome along evolution and its effect on chromatin packing
Authors: Cai Zhicheng , He Yueying , Liu Sirui , Xue Yue , Quan Hui , Zhang Ling , Gao Yi Qin
Published: February 2020

Dinucleotide densities and their distribution patterns vary significantly among species. Previous studies revealed that CpG is susceptible to methylation, enriched at topologically associating domains (TADs) boundaries and its distribution along the genome correlates with chromatin compartmentalization. However, the multi-scale organizations of CpG in the linear genome, their role in chromatin organization, and how they change along the evolution are only partially understood. By comparing the CpG distribution at different genomic length scales, we quantify the difference between the CpG distributions of different species and evaluate how the hierarchical uneven CpG distribution appears in evolution. The clustering of species based on the CpG distribution is consistent with the phylogenetic tree. Interestingly, we found the CpG distribution and chromatin structure to be correlated in many different length scales, especially for mammals and avians, consistent with the mosaic CpG distribution in the genomes of these species.
Selective and controlled myelin formation by individual interfascicular oligodendrocytes in the mouse corpus callosum
Authors: Tanaka Tatsuhide , Ohno Nobuhiko , Osanai Yasuyuki , Saitoh Sei , Thai Truc Quynh , Nishimura Kazuya , Shinjo Takeaki , Takemura Shoko , Tatsumi Kouko , Wanaka Akio
Published: February 2020

Single oligodendrocytes produce myelin sheath around multiple axons in the central nervous system. Interfascicular oligodendrocytes (IOs) in the white matter are aligned in rows and facilitate nerve conduction, but their detailed morphologies remain largely unknown. In the present study, we three-dimensionally reconstructed seven IOs in a row in the murine corpus callosum using serial block face-scanning electron microscopy (SBF-SEM). These morphologically polarized IOs extended a thick process with numerous branches from the cytoplasm-rich part of the cell and formed myelin sheaths preferentially around distant axons. The multiple branched processes of each IO myelinated multiple axons having similar diameters with restricted myelin thicknesses, indicating that individual IOs have their own myelination profiles even on distinct target neurons. Consistent with the finding, the IOs transduced and visualized with the rabies viral vector expressing GFP showed statistically significant variations in the myelination patterns. We further reconstructed the sheath immediately adjacent to those derived from the seven IOs; the thicknesses of both sheaths were significantly correlated despite emanating from different IOs. These results proposed a rule that myelination by individual IOs, regulated by interaction with ensheathed axons, is selective in specific axons and at the same time orchestrated at the whole cell level.

Main points

Callosal oligodendrocytes form myelin sheaths preferentially around distant axons.

Each oligodendrocyte myelinate multiple axons having similar diameters with restricted myelin thicknesses.

The thicknesses of adjacent myelin sheaths are similar.
Two distinct types of eye-head coupling in freely moving mice
Authors: Meyer Arne F. , O’Keefe John , Poort Jasper
Published: February 2020

Animals actively interact with their environment to gather sensory information. There is conflicting evidence about how mice use vision to sample their environment. During head restraint, mice make rapid eye movements strongly coupled between the eyes, similar to conjugate saccadic eye movements in humans. However, when mice are free to move their heads, eye movement patterns are more complex and often non-conjugate, with the eyes moving in opposite directions. Here, we combined eye tracking with head motion measurements in freely moving mice and found that both observations can be explained by the existence of two distinct types of coupling between eye and head movements. The first type comprised non-conjugate eye movements which systematically compensated for changes in head tilt to maintain approximately the same visual field relative to the horizontal ground plane. The second type of eye movements were conjugate and coupled to head yaw rotation to produce a “saccade and fixate” gaze pattern. During head initiated saccades, the eyes moved together in the same direction as the head, but during subsequent fixation moved in the opposite direction to the head to compensate for head rotation. This “saccade and fixate” pattern is similar to that seen in humans who use eye movements (with or without head movement) to rapidly shift gaze but in mice relies on combined eye and head movements. Indeed, the two types of eye movements very rarely occurred in the absence of head movements. Even in head-restrained mice, eye movements were invariably associated with attempted head motion. Both types of eye-head coupling were seen in freely moving mice during social interactions and a visually-guided object tracking task. Our results reveal that mice use a combination of head and eye movements to sample their environment and highlight the similarities and differences between eye movements in mice and humans.

Highlights

Tracking of eyes and head in freely moving mice reveals two types of eye-head coupling

Eye/head tilt coupling aligns gaze to horizontal plane

Rotational eye and head coupling produces a “saccade and fixate” gaze pattern with head leading the eye

Both types of eye-head coupling are maintained during visually-guided behaviors

Eye movements in head-restrained mice are related to attempted head movements
Deep sampling and pooled amplicon sequencing reveals hidden genic variation in heterogeneous rye accessions
Authors: Hawliczek Anna , Bolibok Leszek , Tofil Katarzyna , Borzęcka Ewa , Jankowicz-Cieślak Joanna , Gawroński Piotr , Kral Adam , Till Bradley J , Bolibok-Brągoszewska Hanna
Published: February 2020

Loss of genetic variation negatively impacts breeding efforts and food security. Genebanks house over 7 million accessions representing vast allelic diversity that is a resource for sustainable breeding. Discovery of DNA variations is an important step in the efficient use of these resources. While technologies have improved and costs dropped, it remains impractical to consider resequencing millions of accessions. Candidate genes are known for most agronomic traits, providing a list of high priority targets. Heterogeneity in seed stocks means that multiple samples from an accession need to be evaluated to recover available alleles. To address this we developed a pooled amplicon sequencing approach and applied it to the out-crossing cereal rye(Secale cereale).Ninety-five rye accessions of different improvement status and worldwide origin, each represented by a pooled sample comprising DNA of 96 individual plants, were evaluated for sequence variation in six target genes involved in seed quality, biotic and abiotic stress resistance. Seventy-four predicted deleterious variants were identified using multiple algorithms. Rare variants were recovered including those found only in a low percentage of seed. A large extent of within-population heterogeneity was revealed, providing an important point for consideration during rye germplasm conservation and utilization efforts. We conclude that this approach provides a rapid and flexible method for evaluating stock heterogeneity, probing allele diversity, and recovering previously hidden variation.
The relationship between quality and governance mechanisms
Authors: Martins Saturnina Alves da Silva , Machado Marcio C. , Queiroz Maciel M. , Telles Renato
Published: February 2020

Purpose

Recent literature has highlighted the importance of quality and governance in supply networks. Usually, the relationships between the actors are complex, comprising both formal and informal interactions. Despite recent advances in quality and governance in supply networks, extant literature highlights the lack of quality in healthcare supply-chain networks in relation to governance mechanisms. This paper aims to investigate the role of governance mechanisms and their influence on the quality of healthcare supply networks, and assumes that governance instruments can support quality performance.

Design/methodology/approach

A multiple-case research approach was employed. Six organisations in the Brazilian healthcare sector were analysed (four operate only with renal replacement therapy, one is a material supplier, and one operates with renal replacement therapy and collective procurement).

Findings

Findings showed that there is no formalised supply network structure in these organisations. A possible consequence of this is that the supply-network governance is dominated by informal relationships. In the quality dimension, managers' awareness is limited, but there are mechanisms in place to control the quality of the materials.

Practical implications

Healthcare managers can actively invest in the social aspects of the relationship between buyer and supplier, such as trust and commitment, thus increasing responsiveness in patient care. However, this informal procedure can lead to problems with tracking and reliability, ultimately leading to quality problems. Therefore, it is recommended that formal and informal governance instruments be used jointly to improve service quality.

Originality/value

This study suggests that the integration of formal and informal mechanisms of governance can improve the quality of supply networks. Additionally, if the administrative process is purely formal, network relationships and their efficiency will be impaired.
Strategic issues in supply chain management of Indian SMEs due to globalization: an empirical study
Authors: Singh Rajesh Kumar , Kumar Ravinder
Published: February 2020

Purpose

In globalized market, organizations of all sizes are having huge opportunities for growth. However, due to various resource constraints, it has become challenging for small and medium enterprises (SMEs) of growing economies to survive in this global competition. Effective supply chain management (SCM) can be a major driving factor for success of Indian SMEs in dynamic world economy. SMEs face many operational challenges while implementing effective SCM. The purpose of this paper is to study different strategic issues for successful implementation of SCM in Indian SMEs.

Design/methodology/approach

A survey has been conducted in Indian SMEs of different sectors. Major constructs of survey instrument are motivations, hindrances, investment priorities, supply chain practices and performance. In total, 1,500 Indian SMEs have been approached for collecting response through survey instrument. 257 complete responses were finalized. Statistical analysis of data acquired from survey is performed by using SPSS software.

Findings

It is observed that managing customers, organization resources, and inventory are main SCM practices. Major investment areas are systems for developing quick response and quality management. Currently, human resource and knowledge management have been found to be less priority areas for SMEs. The major focus of Indian SMEs is on cost and lead time reduction by having effective SCM.

Originality/value

Novelty of this study is that strategic issues for effective SCM in context to Indian SMEs have been analyzed. The findings of the study will help Indian SMEs in doing strategic planning for being competitive in the global market.