bluuebunny/crossref_metadata_2025 huggingface dataset:
Expression of Programmed Cell Death Proteins in Kaposi Sarcoma and Cutaneous Angiosarcoma
Authors: Gambichler Thilo , Koim Sonja , Wrobel Malwina , Käfferlein Heiko U. , Brüning Thomas , Stockfleth Eggert , Becker Jürgen C. , Lang Kerstin
Published: March 2020

Not only for cutaneous angiosarcoma (CAS) patients but also for advanced and therapy-refractory patients with classic Kaposi sarcoma (CKS) and human immunodeficiency virus (HIV)-associated Kaposi sarcoma (HIV-KS) there is a high need for more effective treatment modalities. The aim of this work was to study programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) protein expression and related immune parameters in CKS, HIV-KS, and CAS and correlate it with other immunologic parameters and clinical data. Immunohistochemistry was performed on formalin-fixed paraffin-embedded tumor tissue of 19 CKS, 7 HIV-KS, and 12 CAS patients using antibodies against the following (and they are): PD-1, PD-L1, CD4, CD8, CD56, and FOXP3. PD-1 expression significantly correlated with PD-L1 expression Moreover, PD-1 and PD-L1 expression significantly correlated with CD56 and FOXP3 expression. High intratumoral FOXP3 expression was significantly associated with disease relapse (P=0.029). CD4 and FOXP3 expression was significantly higher in CKS and CAS, as compared with HIV-KS. All in all, PD-1 and PD-L1 expression was relatively weak and did not significantly differ between CKS, HIV-KS, and CAS patients. Nevertheless, PD-1 was positive in 31.6% of CKS, 28.6% of HIV-KS, and 33.3% of CAS patients. PD-L1 was expressed in 36.6% of CKS, 28.6% of HIV-KS, and 41.7% of CAS patients. We have provided evidence that PD-1/PD-L1 signalling is of importance in angiosarcomas such as CKS, HIV-KS, and CAS. Our results support the notion that the use of PD-1/PD-L1 inhibitors may represent an effective strategy against these tumors.
Trends in Authorship of Original Scientific Articles in Journal of Glaucoma: An Analysis of 25 Years Since the Initiation of the Journal
Authors: Chien Jason L. , Wu Bernie P. , Nayer Zacharia , Grits Daniel , Rodriguez Geoffrey , Gu Alex , Ghassibi Mark P. , Chien Gwo-Farn , Oliveira Cristiano , Stamper Robert L. , Van Tassel Sarah H. , Muylaert Stephanie , Belyea David A.
Published: March 2020

Précis:

Publications in glaucoma have seen an increase in the number of authors and disclosures per article, authors with dual degrees, and international authors, but contributions of women to articles published remains low.

Purpose:

Authorship trends have been studied across many medical specialties and in ophthalmology as a whole, but not specifically in glaucoma. The authors explored the authorship trends of original scientific articles in the Journal of Glaucoma.

Materials and Methods:

The authors recorded the number of authors and disclosures per article, degree type of first and last authors, geographical origin of the corresponding author, and sex of first and last authors of original content from the Journal of Glaucoma published in 1992, 1997, 2002, 2007, 2012, and 2017.

Results:

A total of 642 articles were analyzed. From 1992 to 2017, annual published articles increased from 38 to 242 (P=0.02), the mean number of authors per article increased from 3.2 to 5.2 (P<0.01), the mean number of disclosures per article increased from 0.3 to 1.0 (P=0.04), the proportion of first and last authors with dual degrees (medical plus advanced degrees) also increased (both P<0.03), whereas the proportion with a sole medical degree decreased (both P<0.05). There was a proportional decrease in articles from North America (P=0.03), and proportional increase from the “Far East” (P=0.04) and “Other” regions (P=0.04). No significant changes in proportions of female first and last authors were found (both P>0.28).

Conclusions:

Consistent with authorship trends across various other medical specialties, glaucoma has seen an increase in the number of authors and disclosures per article, authors with dual degrees, and authors from the “Far East” and “Other” regions. However, contributions of women to articles published in Journal of Glaucoma remain low.
Effect of Pharmacological Pupil Dilatation on Angle Configuration in Untreated Primary Angle Closure Suspects: A Swept Source Anterior Segment Optical Coherence Tomography Study
Authors: Narayanaswamy Arun , Baskaran Mani , Tun Tin A. , Htoon Hla M. , Aung Tin
Published: March 2020

Precis:

Angle-closure worsens with pharmacological dilatation in about 50.0% of the subjects diagnosed as primary angle-closure suspects (PACSs).

Purpose:

The purpose of this study was to evaluate the changes in angle configuration with swept-source anterior segment optical coherence tomography before and after pharmacological pupil dilatation in untreated PACSs.

Patients and Methods:

A total of 106 subjects over the age of 50 years and diagnosed as PACSs were included in this cross-sectional cohort study. 360-degree scans of the angles were captured using swept-source optical coherence tomography before and 1 hour after pharmacological dilatation. The angle scans from swept-source optical coherence tomography were analyzed to calculate the iris-trabecular contact (ITC) index. The main outcome measure was to evaluate the change in ITC index after dilatation. Multivariate linear and logistic regression analysis were performed to identify factors influencing change of ITC index and to identify factors associated with increase in ITC index after dilatation.

Results:

Majority of subjects were Chinese (93.4%) and female (79.2%). The overall mean predilatation ITC index was 45.3% (±23.7) and postdilatation ITC index was 46.05% (±25.9) with a mean change of 0.78% (±16.5; P=0.62). Fifty-three eyes (50.0%) showed an increase in ITC index (angle narrowing) after dilatation. An increase in ITC index was associated with shallower anterior chamber depth (odds ratio: 0.18; 95% confidence interval: 0.04-0.77) and bigger lens vault (odds ratio: 14.31; 95% confidence interval: 1.55-132.34).

Conclusions:

Pharmacological pupil dilatation worsened angle closure in 50.0% of subjects with narrow angles. Shallower anterior chamber and bigger lens vault were associated with greater angle narrowing in these subjects.
Concussion Knowledge and Reporting Behaviors Among Collegiate Athletes
Authors: McAllister-Deitrick Jamie , Beidler Erica , Wallace Jessica , Anderson Morgan
Published: March 2020

Objective:

The purpose of the current study was to explore knowledge surrounding sport-related concussions (SRCs) and the impact on reporting behaviors in collegiate athletes, including sex differences.

Design:

Cross-sectional.

Setting:

Institutional.

Participants:

Participants were 986 collegiate athletes (607 men), aged 19.7 years (SD = 1.4) from 6 institutions, who completed a survey, including items on personal/sport demographics and SRC knowledge and reporting behaviors.

Interventions:

Athletes were given a short (15-minute) survey to complete during team meetings and preparticipation physicals.

Main Outcome Measures:

Athletes' scores on the survey, and reporting behaviors (ie, whether or not they failed to report a suspected SRC and reasons for not reporting SRCs), were examined.

Results:

Independent samples t tests revealed female athletes scored significantly higher than male athletes on total SRC knowledge [t (926.6) = −10.6, P < 0.01] and symptom knowledge (t (859) = −7.0, P < 0.01). Approximately one-quarter of athletes reported continuing to play after sustaining a suspected SRC. Chi-square analyses exposed significant differences between male and female athletes failing to report a suspected SRC (χ2 = 7.69, P < 0.01).

Conclusions:

Given the current findings, educational efforts aimed at collegiate athletes may not be enough. Furthermore, it is apparent that sex differences exist in SRC knowledge and reporting behaviors among collegiate athletes.
Pulsatile Versus Nonpulsatile Flow During Cardiopulmonary Bypass: Extent of Hemolysis and Clinical Significance
Authors: Tan Zihui , Besser Martin , Anderson Simon , Newey Caroline , Iles Ray , Dunning John , Falter Florian
Published: March 2020

Pulsatile flow has been used during cardiopulmonary bypass (CPB) for decades and its use is increasing with advancing extracorporeal technology. Pulsatile flow generates higher circuit pressures and shear forces than nonpulsatile flow at comparable pump flow and patient mean arterial pressure. Very little is known about the effect this has on erythrocytes. We included 62 adult patients (32 in the pulsatile group and 30 in the nonpulsatile group) undergoing elective coronary artery bypass grafting in this prospective observational study. Blood samples were collected at routine sampling times throughout surgery and were analyzed for the presence of free heme and globin using mass spectroscopy. Patient characteristics, CPB, and aortic cross-clamp times, pump flow as well as patient mean arterial pressure were similar in both groups. Maximum circuit pressure in the pulsatile flow group was statistically significantly higher than that in the nonpulsatile flow group (257.12 vs. 190.64 mmHg, p < 0.0001). Both heme and globin levels were higher in the pulsatile flow group. This reached statistical significance with globin at 30 minutes of CPB and with heme after aortic unclamping. We conclude that pulsatile CPB using roller pumps results in a greater extent of hemolysis. The clinical significance, however, is not yet known.
Veterinary Pet Supplements and Nutraceuticals
Authors: Finno Carrie J.
Published: March 2020

Veterinary pet supplements and nutraceuticals are widely used by dog, cat, and horse owners across the United States, generating millions of dollars in revenue for manufacturers. Despite the widespread use of these veterinary products, oversight and regulation remain limited as compared with human dietary supplement regulations. This review describes the current regulation, quality control, safety, and efficacy of pet supplements and nutraceuticals targeted toward dogs, cats, and horses.
An Overlap Between “Ultraprocessed” Foods and the Preexisting Nutrient Rich Foods Index?
Authors: Drewnowski Adam , Gupta Shilpi , Darmon Nicole
Published: March 2020

The category of “ultraprocessed” foods in the NOVA food classification scheme is ostensibly based on industrial processing. We compared NOVA category assignments with the preexisting family of Nutrient Rich Food (NRF) indices, first developed in 2004. The NRF indices are composed of 2 subscores: the positive NR based on protein, fiber, and vitamins and minerals, and the negative LIM subscore based on saturated fat, added sugars, and sodium. The 378 foods that were components of the widely used Fred Hutchinson Cancer Center food frequency questionnaire were assigned to NOVA categories and scored using multiple NRF indices. Contrary to published claims, NOVA was largely based on the foods' content of saturated fat, added sugars, and sodium. There were strong similarities between NOVA categories and NRF scores that were largely driven by the nutrients to limit. Nutrient density led to higher increased NRF scores but had less impact on NOVA categories. As a result, the NOVA scheme misclassified some nutrient-rich foods. We conclude that the NOVA classification scheme adds little to the preexisting nutrient profiling models. The purported links between NOVA categories and health outcomes could have been obtained using preexisting NRFn.3nutrient density metrics.
The Balancing Act—Nutrition and Sustainability
Authors: Smith Edge Marianne
Published: March 2020

The goal to find sustainable solutions that will produce more and better food with less land, less water, and less labor for years to come is at the forefront of today's food value chain. Numerous academic institutions, food and agriculture organizations, and consumers are focused on addressing this issue, but differences do exist, reflecting a lack of scientific consensus. This article examines conflicts of the sustainability conversation between the “haves” and the “have nots” when it comes to food and especially who should eat more and who less and discusses the challenges of research studies when measuring the impact of diet on environment. Even though the reduction of animal protein intake is the only predictive outcome of many modeling studies, there are others, such as how human health outcomes are evaluated in concert with environmental health and economics, that are equally important factors that must be assessed, especially when comparing studies with each other. The one constant theme is clear—no single solution will address our food system sustainability conundrum without unintended consequences on one or another factor. If we, as a society, are truly committed to providing sustainable diets that are nutrient-dense, affordable, culturally appropriate, and respectful of the environment, collaboration and consensus building among all participants in the total food system are essential.
Hip fracture systems—European experience
Authors: Chesser Tim J.S. , Inman Dominic , Johansen Antony , Belluati Alberto , Pari Carlotta , Contini Achille , Voeten Stijn.C. , Hegeman Johannes H. , Ponsen Kornelis J. , Montero-Fernández Nuria , Delgado-Martínez Alberto , Chana-Rodríguez Francisco
Published: March 2020

European countries have established health care systems but are struggling with the increasing rise of fragility fractures in their aging population. In trying to address this significant burden, countries are establishing national guidelines and standards, focusing on hip fractures, which represent the significant cost for this patient group. This has evolved with the establishment of national audits and guidelines. Reports from 4 European countries (England, Italy, Netherlands, and Spain) are presented. All nations have identified both deficiencies in their systems, and protocols to improve these deficiences. When standards are introduced, there has been evidence of improved results. Significantly more work is needed to understand the key components of the systems and pathways, and efforts to study and standardize care are ongoing.
Hardware considerations in infection and nonunion management
Authors: Hoit Graeme , Bonyun Marissa , Nauth Aaron
Published: March 2020

The occurrence of both nonunion and fracture-related infection provides challenges for both the patient and the treating orthopaedic surgeon, with the potential need for complex reconstructive procedures to achieve union and/or eradicate infection. In addition to addressing the multiple different factors that often contribute to nonunion, surgeons are often forced to deal with difficult hardware issues at the time of revision surgery including infected hardware, loose or failing hardware, malaligned hardware, or inappropriate hardware constructs. This article reviews common causes of nonunions with emphasis on infection management and provides indications and techniques for hardware removal in the context of an algorithmic approach to nonunion management with illustrative case examples.
Managing bone loss in open fractures
Authors: Adamczyk Andrew , Meulenkamp Bradley , Wilken Geoffrey , Papp Steven
Published: March 2020

Segmental bone loss continues to pose substantial clinical and technical challenges to orthopaedic surgeons. While several surgical options exist for the treatment of these complex patients, there is not a clear consensus or specific guidelines on the optimal management of these injuries as a whole. Many factors must be taken into consideration when planning surgery for these individuals. In order for these techniques to yield optimal results, each injury must be approached in a step-wise and multidisciplinary fashion to ensure that care is taken in bone and wound bed preparation, that soft tissues are healthy and free of contaminants, and that the patient's medical condition has been optimized. Through this article, we will answer relevant questions and discuss common obstacles and challenges encountered with these complex injuries. We will also review the many treatment options available or in development to address this problem.
Hip fracture care and national systems in Israel and South Africa
Authors: Weil Yoram A. , Bernstein Brian P. , Maqungo Sithombo , Khoury Amal , Liebergall Meir , Laubscher Maritz
Published: March 2020

Despite the same latitude on earth, Israel and South Africa have a wide variety of healthcare systems and approaches. Israel is a developed country with life expectancy within the first decile of the modern world. South Africa is a developing country where available resources and health care varies greatly across the country. Israeli policy makers have realized in 1999 the importance of early surgery for hip fractures as the single most important factor contributing to decreased mortality. After an introduction of a newer reimbursement system in 2004, and public advertising of early hip fracture treatment as a quality tag for hospitals, in more than 85% of the cases patients are operated on early (within 8 hours) with a significant decrease in mortality. However, other issues such as patient preparation, rehabilitation, and prevention are still at their beginning. South Africa deals with significant challenges with high energy hip fractures in a younger population, although osteoporosis is on the rise in certain parts of the country. Due to limited resources and distances, time to surgery differs among hospital systems in the country. In public hospitals, a delay up to a week may be common, whereas in private hospitals most patients are operated early within 48 to 72 hours. Due to decreased life expectancy, arthroplasty is more aggressively used in displaced femoral neck fractures. Rehabilitation is mostly done within the families. Prevention and orthogeriatric teamwork are not being commonly practiced. Generally speaking, more attention to hip fractures is needed from healthcare funders.
Antibiotic utilization in open fractures
Authors: Atwan Yousif , Miclau Theodore , Schemitsch Emil H. , Teague David
Published: March 2020

Open fractures are complex presentations with elevated risks of infection and nonunion due to a multitude of factors. Along with early surgical debridement, antibiotics have been heavily utilized and have become part of standard of care to reduce the risks of fracture-related infections. Many aspects of their use have been studied and debated. The early administration of intravenous antibiotics has been shown to significantly reduce the incidence of infection. Furthermore, current standards do not recommend prolonged antibiotic administration post wound closure. Recently, an increasing number of studies have assessed the utility of locally administered antibiotics. Clinical and basic science studies have been relatively supportive of their usage, but further studies are still warranted to further delineate their effects.
Hospital Readmission and Mortality in a Brazilian Tertiary Public Hospital
Authors: Bettiol Augusto Berton , Wajner André , Pivatto Júnior Fernando
Published: March 2020

Background and Objectives:

Data on mortality associated with hospital readmission are imprecise and highly variable. This study aimed to describe the rate of nonelective 30-day readmission and associated hospital mortality of patients discharged from the Internal Medicine Unit of a Brazilian tertiary public hospital.

Methods:

This retrospective cohort study included all patients discharged from the Internal Medicine Unit of our institution between September and November 2017 who were nonelectively readmitted within 30 days.

Results:

A total of 1047 hospital discharges were analyzed. The rate of nonelective 30-day readmission was 13.7%. Of these, 41 (28.5%) were early readmissions (0-7 days) and 103 (71.5%) were late readmissions (8-30 days). The hospital mortality rate during readmission was 27.8%, being significantly higher during early readmissions (41.5% vs 22.3%; P = .035). Early (as compared with late) readmission was associated with mortality during readmission (relative risk [RR] 1.95; 95% confidence interval, 1.18-3.22; P = .002), regardless of age and Charlson comorbidity index.

Conclusion:

The Readmission rate was 13.7%, with an associated mortality of 27.8%. Early readmission was an independent predictor of mortality (RR 1.95) in relation to late readmission. Larger studies are needed to better identify this group of patients with an aim to adopt preventive measures.
Variability and Standardization of Quantitative Imaging
Authors: Hagiwara Akifumi , Fujita Shohei , Ohno Yoshiharu , Aoki Shigeki
Published: March 2020

Radiological images have been assessed qualitatively in most clinical settings by the expert eyes of radiologists and other clinicians. On the other hand, quantification of radiological images has the potential to detect early disease that may be difficult to detect with human eyes, complement or replace biopsy, and provide clear differentiation of disease stage. Further, objective assessment by quantification is a prerequisite of personalized/precision medicine. This review article aims to summarize and discuss how the variability of quantitative values derived from radiological images are induced by a number of factors and how these variabilities are mitigated and standardization of the quantitative values are achieved. We discuss the variabilities of specific biomarkers derived from magnetic resonance imaging and computed tomography, and focus on diffusion-weighted imaging, relaxometry, lung density evaluation, and computer-aided computed tomography volumetry. We also review the sources of variability and current efforts of standardization of the rapidly evolving techniques, which include radiomics and artificial intelligence.
Influence of MRI Examinations on Animal Welfare and Study Results
Authors: Baier Jasmin , Rix Anne , Drude Natascha Ingrid , Darguzyte Milita , Baues Maike , May Jan-Niklas , Schipper Sandra , Möckel Diana , Palme Rupert , Tolba René , Kiessling Fabian
Published: March 2020

Objectives

Magnetic resonance imaging (MRI) is considered to be well tolerated by laboratory animals. However, no systematic study has been performed yet, proving this assumption. Therefore, the aim of this study was to investigate the possible effects of longitudinal native and contrast-enhanced (CE) 1-T and 7-T MRI examinations on mouse welfare as well as 4T1 breast cancers progression and therapy response.

Material and Methods

Forty-seven healthy and 72 breast cancer-bearing mice (4T1) were investigated. One-Tesla (ICON) and 7-T (Biospec) MRI measurements were performed thrice per week under isoflurane anesthesia in healthy BALB/c mice for 4 weeks and 3 times within 2 weeks in tumor-bearing animals. Animal welfare was examined by an observational score sheet, rotarod performance, heart rate measurements, and assessment of fecal corticosterone metabolites. Furthermore, we investigated whether CE-MRI influences the study outcome. Therefore, hemograms and organ weights were obtained, and 4T1 tumor growth, perfusion, immune cell infiltration, as well as response to the multikinase inhibitor regorafenib were investigated. Statistical comparisons between groups were performed using analysis of variance and Tukey or Bonferroni post hoc tests.

Results

Mice showed no alterations in the observational score sheet rating, rotarod performance, heart rate, and fecal corticosterone metabolites (P > 0.05) after repeated MRI at both field strengths. However, spleen weights were reduced in all healthy mouse groups that received isoflurane anesthesia (P < 0.001) including the groups investigated by 1-T and 7-T MRI (P = 0.02). Neither tumor progression nor response to the regorafenib treatment was affected by isoflurane anesthesia or CE-MRI monitoring. Furthermore, immunohistological tumor analysis did not indicate an effect of isoflurane and MRI on macrophage infiltration of tumors, perfusion of tumor vessels, and apoptotic cell rate (P > 0.05).

Conclusions

Repeated MRI did not influence the welfare of mice and did not affect tumor growth and therapy response of 4T1 tumors. However, systemic immunological effects of isoflurane anesthesia need to be considered to prevent potential bias.
Congenital Zika Syndrome
Authors: Gaba Ann , Soliman Ghada A.
Published: March 2020

Zika infection of pregnant women can result in infants with microcephaly and other severe birth defects. With these conditions come a variety of challenges that impair nutritional status. While Zika infection in the United States remains relatively rare, registered dietitian nutritionists should be prepared to assess and provide support to affected children. The most common nutrition-related consequences of Zika infection have some possible nutrition interventions to minimize their impact. The goal of nutritional care for infants and children with congenital Zika syndrome is to promote optimal functional capacity and quality of life.
Culturally Adapted, Hands-on Malnutrition Workshop for Dietitians in Ghana Increases Self-efficacy, Knowledge, and Skills
Authors: Wright Lauri , Marrero Alana , Thompson Leslie , Zeola Sarah , Boateng Laurene , Epps James , Lewis Sherri
Published: March 2020

Malnutrition is a major public health concern in Ghana where 7.5% of women are underweight and one-third of child deaths are attributed to malnutrition. Implementation of a malnutrition diagnosis offers a potential, cost-effective solution to improve a patient's health outcome. This report describes a hands-on workshop on the Academy of Nutrition and Dietetics/American Society for Parenteral and Enteral Nutrition Malnutrition Guidelines designed for Ghanaian dietitians. The teaching techniques and cultural adaptation are detailed. Program evaluation demonstrated that the workshop improved knowledge, application skills, and confidence among the participants.
Nutrition Management for the Preterm Infant With PAH Deficiency
Authors: Barr Emily M. , Weihe Tarine U. , Hillsman Lori A. , Rowzer Kasey D. , McGinty Lindsey , Heese Bryce A. , Gannon Jennifer L.
Published: March 2020

The nutrition guidelines for management of phenylketonuria (PKU or phenylalanine hydroxlyase [PAH] deficiency) are well developed. One missing component is the phenylalanine (Phe) requirements for the preterm infant with PAH deficiency. It has been found that preterm infants at a postmenstrual age (PMA) of 30 and 32 weeks have required a Phe intake as high as 100 mg/kg, well above the current clinical guidelines available for the term infant. Three case presentations illustrate modifications that the clinician may need to consider when caring for the preterm infant with PAH deficiency during the weeks leading up to 40 weeks of PMA.
The Neurophysiological Severity of Carpal Tunnel Syndrome Cannot Be Predicted by Median Nerve Cross-Sectional Area and Wrist-to-Forearm Ratio
Authors: Martikkala Lauri , Himanen Sari-Leena , Virtanen Katja , Mäkelä Katri
Published: March 2020

Purpose:

The median nerve cross-sectional area at the wrist (CSA) and the wrist-to-forearm ratio of the cross-sectional areas (WFR) are ultrasound parameters used in the diagnosis and grading of carpal tunnel syndrome. This study aimed to determine the diagnostic accuracy of the CSA and WFR as well as to compare their diagnostic value.

Methods:

A retrospective evaluation was conducted of a cohort of 218 patients who had undergone nerve conduction studies (NCSs) and an ultrasound of the median nerve. The examined wrists were classified into an NCS negative and three NCS positive (mild, moderate, and severe) categories. The CSA and WFR were compared across the categories.

Results:

The CSA and WFR were significantly smaller in the NCS negative category than in the NCS positive categories. The WFR was significantly smaller in the mild category than in the moderate category. The CSA could not be used to differentiate across the NCS positive categories.

Conclusions:

The CSA and WFR are satisfactorily reliable in detecting carpal tunnel syndrome, but they cannot be considered as surrogate indicators of electrophysiological severity.
Arthrobacter bussei sp. nov., a pink-coloured organism isolated from cheese made of cow’s milk
Authors: Flegler Alexander , Runzheimer Katharina , Kombeitz Vanessa , Mänz Anna Tatjana , Heidler von Heilborn David , Etzbach Lara , Schieber Andreas , Hölzl Georg , Hüttel Bruno , Woehle Christian , Lipski André
Published: March 2020

A pink-coloured bacterium (strain KR32T) was isolated from cheese and assigned to the ‘Arthrobacter agilisgroup’. Members of the ‘pinkArthrobacter agilisgroup’ form a stable clade (100 % bootstrap value) and contain the speciesArthrobacter agilis,Arthrobacter ruberandArthrobacter echini, which share ≥99.0 % 16S rRNA gene sequence similarity. Isolate KR32Tshowed highest 16S rRNA gene sequence similarity (99.9 %) toA. agilisDSM 20550T. Additional multilocus sequence comparison confirmed the assignment of strain KR32Tto the clade ‘pinkA. agilisgroup’. Average nucleotide identity and digital DNA–DNA hybridization values between isolate KR32TandA. agilisDSM 20550Twere 82.85 and 26.30 %, respectively. The G+C content of the genomic DNA of isolate KR32Twas 69.14 mol%. Chemotaxonomic analysis determined anteiso-C15 : 0as the predominant fatty acid and MK-9(H2) as the predominant menaquinone. Polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylinositol and monoacyldimannosyl-monoacylglycerol. The peptidoglycan type of the isolate was A3α. The carotenoid bacterioruberin was detected as the major pigment. At 10 °C, strain KR32Tgrew with increased concentrations of bacterioruberin and production of unsaturated fatty acids. Strain KR32Twas a Gram-stain-positive, catalase-positive, oxidase-positive and coccus-shaped bacterium with optimal growth at 27–30 °C and pH 8. The results of phylogenetic and phenotypic analyses enabled the differentiation of the isolate from other closely related species of the ‘pinkA. agilisgroup’. Therefore, strain KR32Trepresents a novel species for which the nameArthrobacter busseisp. nov. is proposed. The type strain is KR32T(=DSM 109896T=LMG 31480T=NCCB 100733T).
Genetic Profiles in Pharmacogenes Indicate Personalized Drug Therapy for COVID-19
Authors: Wang Lei-Yun , Cui Jia-Jia , OuYang Qian-Ying , Zhan Yan , Wang Yi-Min , Xu Xiang-Yang , Guo Cheng-Xian , Yin Ji-Ye
Published: March 2020

Background

The coronavirus disease 2019 (COVID-19) has become a global pandemic currently. Many drugs showed potential for COVID-19 therapy. However, genetic factors which can lead to different drug efficiency and toxicity among populations are still undisclosed in COVID-19 therapy.

Methods

We selected 67 potential drugs for COVID-19 therapy (DCTs) from clinical guideline and clinical trials databases. 313 pharmaco-genes related to these therapeutic drugs were included. Variation information in 125,748 exomes were collected for racial differences analyses. The expression level of pharmaco-genes in single cell resolution was evaluated from single-cell RNA sequencing (scRNA-seq) data of 17 healthy adults.

Results

Pharmacogenes, including CYP3A4, ABCB1, SLCO1B1, ALB, CYP3A5, were involved in the process of more than multi DCTs. 224 potential drug-drug interactions (DDIs) of DCTs were predicted, while 112 of them have been reported. Racial discrepancy of common nonsynonymous mutations was found in pharmacogenes including: VDR, ITPA, G6PD, CYP3A4 and ABCB1 which related to DCTs including ribavirin, α-interferon, chloroquine and lopinavir. Moreover, ACE2, the target of 2019-nCoV, was only found in parts of lung cells, which makes drugs like chloroquine that prevent virus binding to ACE2 more specific than other targeted drugs such as camostat mesylate.

Conclusions

At least 17 drugs for COVID-19 therapy with predictable pharmacogenes should be carefully utilized in risk races which are consisted of more risk allele carriers. At least 29 drugs with potential of DDIs are reported to be affected by other DDIs, they should be replaced by similar drugs without interaction if it is possible. Drugs which specifically targeted to infected cells with ACE2 such as chloroquine are preferred in COVID-19 therapy.
What is required to prevent a second major outbreak of the novel coronavirus SARS-CoV-2 upon lifting the metropolitan-wide quarantine of Wuhan city, China
Authors: Zhang Lei , Shen Mingwang , Ma Xiaomeng , Su Shu , Gong Wenfeng , Wang Jing , Tao Yusha , Zou Zhuoru , Zhao Rui , Lau Joseph , Li Wei , Liu Feng , Ye Kai , Wang Youfa , Zhuang Guihua , Fairley Christopher K
Published: March 2020

Background

The Chinese government implemented a metropolitan-wide quarantine of Wuhan city on 23rd January 2020 to curb the epidemic of the coronavirus COVID-19. Lifting of this quarantine is imminent. We modelled the effects of two key health interventions on the epidemic when the quarantine is lifted.

Method

We constructed a compartmental dynamic model to forecast the trend of the COVID-19 epidemic at different quarantine lifting dates and investigated the impact of different rates of public contact and facial mask usage on the epidemic.

Results

We estimated that at the end of the epidemic, a total of 65,572 (46,156-95,264) individuals would be infected by the virus, among which 16,144 (14,422-23,447, 24.6%) would be infected through public contacts, 45,795 (32,390-66,395, 69.7%) through household contact, 3,633 (2,344-5,865, 5.5%) through hospital contacts (including 783 (553-1,134) non-COVID-19 patients and 2,850 (1,801-4,981) medical staff members). A total of 3,262 (1,592-6,470) would die of COVID-19 related pneumonia in Wuhan. For an early lifting date (21st March), facial mask needed to be sustained at a relatively high rate (≥85%) if public contacts were to recover to 100% of the pre-quarantine level. In contrast, lifting the quarantine on 18th April allowed public person-to-person contact adjusted back to the pre-quarantine level with a substantially lower level of facial mask usage (75%). However, a low facial mask usage (<50%) combined with an increased public contact (>100%) would always lead a significant second outbreak in most quarantine lifting scenarios. Lifting the quarantine on 25th April would ensure a smooth decline of the epidemics regardless of the combinations of public contact rates and facial mask usage.

Conclusion

The prevention of a second epidemic is viable after the metropolitan-wide quarantine is lifted but requires a sustaining high facial mask usage and a low public contact rate.
Improved deep learning model for differentiating novel coronavirus pneumonia and influenza pneumonia
Authors: Zhou Min , Chen Yong , Yang Dexiang , Xu Yanping , Yao Weiwu , Huang Jingwen , Jin Xiaoyan , Pan Zilai , Tan Jingwen , Wang Lan , Xia Yihan , Zou Longkuan , Xu Xin , Wei Jingqi , Guan Mingxin , Feng Jianxing , Zhang Huan , Qu Jieming
Published: March 2020

Background

Chest CT had high sensitivity in diagnosing novel coronavirus pneumonia (NCP) at early stage, giving it an advantage over nucleic acid detection in time of crisis. Deep learning was reported to discover intricate structures from clinical images and achieve expert-level performance in medical image analysis. To develop and validate an integrated deep learning framework on chest CT images for auto-detection of NCP, particularly focusing on differentiating NCP from influenza pneumonia (IP).

Methods

35 confirmed NCP cases were consecutively enrolled as training set from 1138 suspected patients in three NCP designated hospitals together with 361 confirmed viral pneumonia patients from center one including 156 IP patients, from May, 2015 to February, 2020. The external validation set enrolled 57 NCP patients and 50 IP patients from eight centers.

Results

96.6% of NCP lesions were larger than 1 cm and 76.8% were with intensity below –500 Hu, indicating less consolidation than IP lesions which had nodules ranging 5-10 mm. The classification schemes accurately distinguished NCP and IP lesions with area under the receiver operating characteristic curve (AUC) above 0.93. The Trinary scheme was more device-independent and consistent with specialists than the Plain scheme, which achieved a F1 score of 0.847, higher than the Plain scheme (0.774), specialists (0.785) and residents (0.644).

Conclusions

Our study potentially provides an accurate early diagnosis tool on chest CT for NCP with high transferability, and shows high efficiency in differentiating NCP and IP, helping to reduce misdiagnosis and contain the pandemic transmission.
Effects of hypertension, diabetes and coronary heart disease on COVID-19 diseases severity: a systematic review and meta-analysis
Authors: Chen Yingyu , Gong Xiao , Wang Lexun , Guo Jiao
Published: March 2020

Background

COVID-19 patients with chronic diseases such as hypertension, diabetes and coronary heart diseases is more likely to worsen, but with mixed results for COVID-19 severity. This meta-analysis is to analyze the correlation between hypertension, diabetes, coronary heart disease and COVID-19 disease severity.

Methods

Available data from PubMed, Web of Science, China National Knowledge Infrastructure Database, WanFang Database and VIP Database, were analyzed using a fixed effects model meta-analysis to derive overall odds ratios (OR) with 95% CIs. Funnel plots and Begg’s were used to assess publication bias.

Findings

Of 182 articles found following our initial search, we assessed 34 full-text articles, of which 9 articles with 1936 COVID-19 patients met all selection criteria for our meta-analysis. No significant heterogeneity between studies. There were significant correlations between COVID-19 severity and hypertension [OR=2.3 [95% CI (1.76, 3.00), P<0.01], diabetes [OR=2.67, 95% CI (1.91, 3.74), P<0.01], coronary heart disease [OR=2.85 [95% CI (1.68, 4.84), P<0.01]. Most of the studies in the funnel plot are on the upper part and few on the base part, and are roughly symmetrical left and right. Begg’s test: hypertension (Z=-0.1, P=1.0), diabetes (Z=0.73, P=0.466), coronary heart disease (Z=0.38, P=0.707), all found no publication bias.

Interpretation

Hypertension, diabetes, and coronary heart disease can affect the severity of COVID-19. It may be related to the imbalance of angiotensin-converting enzyme 2 (ACE2) and the cytokine storm induced by Glucolipid metabolic disorders (GLMD).

Funding

National Natural Science Foundation of China (No. 81830113, 81530102); Major basic and applied basic research projects of Guangdong Province of China (No. 2019B030302005); National key R & D plan “Research on modernization of traditional Chinese medicine” (No. 2018YFC1704200) and Natural Science Foundation of Guangdong Province (No. 2018A030313391)
A Machine Learning Model Reveals Older Age and Delayed Hospitalization as Predictors of Mortality in Patients with COVID-19
Authors: Sarkar Jit , Chakrabarti Partha
Published: March 2020

Objective

The recent pandemic of novel coronavirus disease 2019 (COVID-19) is increasingly causing severe acute respiratory syndrome (SARS) and significant mortality. We aim here to identify the risk factors associated with mortality of coronavirus infected persons using a supervised machine learning approach.

Research Design and Methods

Clinical data of 1085 cases of COVID-19 from 13th January to 28th February, 2020 was obtained from Kaggle, an online community of Data scientists. 430 cases were selected for the final analysis. Random Forest classification algorithm was implemented on the dataset to identify the important predictors and their effects on mortality.

Results

The Area under the ROC curve obtained during model validation on the test dataset was 0.97. Age was the most important variable in predicting mortality followed by the time gap between symptom onset and hospitalization.

Conclusions

Patients aged beyond 62 years are at higher risk of fatality whereas hospitalization within 2 days of the onset of symptoms could reduce mortality in COVID-19 patients.
Personalized prediction of rehabilitation outcomes in multiple sclerosis: a proof-of-concept using clinical data, digital health metrics, and machine learning
Authors: Kanzler Christoph M. , Lamers Ilse , Feys Peter , Gassert Roger , Lambercy Olivier
Published: March 2020

Background

A personalized prediction of upper limb neurorehabilitation outcomes in persons with multiple sclerosis (pwMS) promises to optimize the allocation of therapy and to stratify individuals for resource-demanding clinical trials. Previous research identified predictors on a population level through linear models and clinical data, including conventional assessments describing sensorimotor impairments. The objective of this work was to explore the feasibility of providing an individualized and more accurate prediction of rehabilitation outcomes in pwMS by leveraging non-linear machine learning models, clinical data, and digital health metrics characterizing sensorimotor impairments.

Methods

Clinical data and digital health metrics were recorded from eleven pwMS undergoing neurorehabilitation. Machine learning models were trained on data recorded pre-intervention. The dependent variables indicated whether a considerable improvement on the activity level was observed across the intervention or not (binary classification), as defined by the Action Research Arm Test (ARAT), Box and Block Test (BBT), or Nine Hole Peg Test (NHPT).

Results

In a cross-validation, considerable improvements in ARAT or BBT could be accurately predicted (94% balanced accuracy) by only relying on patient master data. Considerable improvements in NHPT could be accurately predicted (89% balanced accuracy), but required knowledge about sensorimotor impairments. Assessing these with digital health metrics instead of conventional scales allowed increasing the balanced accuracy by +17% . Non-linear machine-learning models improved the predictive accuracy for the NHPT by +25% compared to linear models.

Conclusions

This work demonstrates the feasibility of a personalized prediction of upper limb neurorehabilitation outcomes in pwMS using multi-modal data collected before neurorehabilitation and machine learning. Information from digital health metrics about sensorimotor impairment was necessary to predict changes in dexterous hand control, thereby underlining their potential to provide a more sensitive and fine-grained assessment than conventional scales. Non-linear models outperformed ones, suggesting that the commonly assumed linearity of neurorehabilitation is oversimplified.

clinicaltrials.govregistration number:NCT02688231
The effects of exposure to predators on personality and plasticity
Authors: Bucklaew Amy , Dochtermann Ned
Published: March 2020

Past experiences are known to affect average behavior but effects on “animal personality”, and plasticity are less well studied. To determine whether experience with predators influences these aspects, we compared the behavior ofGryllodes sigillatusbefore and after exposure to live predators. We found that emergence from shelter and distance moved during open-field trials (activity) changed after exposure, with individuals becoming less likely to emerge from shelters but more active when deprived of shelter. We also found that plasticity in activity increased after exposure to predators and some indications that differences among individuals (i.e. “personality”) in emergence from shelter and the amount of an arena investigated increased after exposure. Our results demonstrate that experience with predators affects not only the average behavior of individuals but also how individuals differ from each other—and their own prior behavior—even when all individuals have the same experiences.
Early prediction of high risk gestational diabetes mellitus via machine learning models
Authors: Wu Yan-Ting , Zhang Chen-Jie , Mol Ben Willem , Li Cheng , Chen Lei , Wang Yu , Sheng Jian-Zhong , Fan Jian-Xia , Shi Yi , Huang He-Feng
Published: March 2020

Aims

Gestational diabetes mellitus (GDM) is a pregnancy-specific disorder that can usually be diagnosed after 24 gestational weeks. So far, there is no accurate method to predict GDM in early pregnancy.

Methods

We collected data extracted from the hospital’s electronic medical record system included 73 features in the first trimester. We also recorded the occurrence of GDM, diagnosed at 24-28 weeks of pregnancy. We conducted a feature selection method to select a panel of most discriminative features. We then developed advanced machine learning models, using Deep Neural Network (DNN), Support Vector Machine (SVM), K-Nearest Neighboring (KNN), and Logistic Regression (LR), based on these features.

Results

We studied 16,819 women (2,696 GDM) and 14,992 women (1,837 GDM) for the training and validation group. DNN, SVM, KNN, and LR models based on the 73-feature set demonstrated the best discriminative power with corresponding area under the curve (AUC) values of 0.92 (95%CI 0.91, 0.93), 0.82 (95%CI 0.81, 0.83), 0.63 (95%CI 0.62, 0.64), and 0.85 (95%CI 0.84, 0.85), respectively. The 7-feature (selected from the 73-feature set) DNN, SVM, KNN, and LR models had the best discriminative power with corresponding AUCs of 0.84 (95%CI 0.83, 0.84), 0.69 (95%CI 0.68, 0.70), 0.68 (95%CI 0.67, 0.69), and 0.84 (95% CI 0.83, 0.85), respectively. The 7-feature LR model had the best Hosmer-Lemeshow test outcome. Notably, the AUCs of the existing prediction models did not exceed 0.75.

Conclusions

Our feature selection and machine learning models showed superior predictive power in early GDM detection than previous methods; these improved models will better serve clinical practices in preventing GDM.

Research in Context section

Evidence before this study

A hysteretic diagnosis of GDM in the 3rd trimester is too late to prevent exposure of the embryos or fetuses to an intrauterine hyperglycemia environment during early pregnancy.

Prediction models for gestational diabetes are not uncommon in previous literature reports, but laboratory indicators are rarely involved in predictive indicators.

The penetration of AI into the medical field makes us want to introduce it into GDM predictive models.

What is the key question?

Whether the GDM prediction model established by machine learning has the ability to surpass the traditional LR model?

Added value of this study

Using machine learning to select features is an effective method.

DNN prediction model have effective discrimination power for predicting GDM in early pregnancy, but it cannot completely replace LR. KNN and SVM are even worse than LR in this study.

Implications of all the available evidence

The biggest significance of our research is not only to build a prediction model that surpasses previous ones, but also to demonstrate the advantages and disadvantages of different machine learning methods through a practical case.