bluuebunny/crossref_metadata_2025 huggingface dataset:
Social Determinants of Health and Patient Safety: An Analysis of Patient Safety Event Reports Related to Limited English-Proficient Patients
Authors: Benda Natalie C. , Wesley Deliya B. , Nare Matthew , Fong Allan , Ratwani Raj M. , Kellogg Kathryn M.
Published: March 2020

Background

Racial and ethnic disparities in healthcare safety have persisted for decades, particularly for patients with language barriers. Previous studies have investigated the frequency and nature of safety events impacting patients with language barriers; others have proposed solutions to fix them. A gap analysis, however, of how we are currently addressing safety issues and why these efforts have not been effective is lacking.

Method

This analysis uses reports from a patient safety event reporting system. Reports contain information regarding no-harm (near miss) events and events where harm may have reached the patient. Reports occurring with patients with a preferred language other than English were extracted and analyzed to determine whether the language barrier contributed to the safety event, the language barrier was mentioned in the resolution, and themes were mentioned for addressing language barriers.

Results

A subset of 1553 events pertaining to non-English–speaking patients were first categorized as “likely” (3%), “plausibly” (10%), or “unlikely” (87%) related to the patient’s language barrier. Second, events related to the patient’s language barrier were categorized as directly addressing (19%), indirectly addressing (3%), not mentioning (69%) the language barrier, or containing insufficient information to determine whether the language barrier was addressed (7%). Third, thematic analysis revealed that the most common methods for addressing language barriers included presenting issues to interpreter services and subsequent use of interpreter services.

Conclusions

This study found that it is challenging to determine the direct role of certain social determinants of health (e.g., language barriers) in safety events. In many cases, the language barrier was not addressed in the event report. Furthermore, when the language barrier was addressed, solution themes typically involved weaker, less sustainable suggested actions.
A Systematic Review of Methods for Medical Record Analysis to Detect Adverse Events in Hospitalized Patients
Authors: Klein Dorthe O. , Rennenberg Roger J.M.W. , Koopmans Richard P. , Prins Martin H.
Published: March 2020

Objective

In this systematic review, we evaluate 2 of the most used trigger tools according to the criteria of the World Health Organization for evaluating methods.

Methods

We searched Embase, PubMed, and Cochrane databases for studies (2000–2017). Studies were included if medical record review (MRR) was performed with either the Global Trigger Tool or the Harvard Medical Practice Study in a hospital population. Quality assessment was performed in duplicate. Fifty studies were included, and results were reported for every criterion separately.

Results

Medical record review reveals more adverse events (AEs) than any other method. However, at the same time, it detects different AEs. The costs of an AE were on average €4296. Considerable efforts have been made worldwide in health care to improve safety and to reduce errors. These have resulted in some positive effects. The literature showed that MRR is focused on several domains of quality of care and seems suitable for both small and large cohorts. Furthermore, we found a moderate to substantial agreement for the presence of a trigger and a moderate to good agreement for the presence of an AE.

Conclusions

Medical record review with a trigger tool is a reasonably well-researched method for the evaluation of the medical records for AEs. However, looking at the World Health Organization criteria, much research is still lacking or of moderate quality. Especially for the cost of detecting AEs, valuable information is missing. Moreover, knowledge of how MRR changes quality and safety of care should be evaluated.
Patient Safety Education 20 Years After the Institute of Medicine Report: Results From a Cross-sectional National Survey
Authors: Arora Sonal , Tsang Fiona , Kekecs Zoltan , Shah Nisha , Archer Stephanie , Smith Jason , Darzi Ara
Published: March 2020

Objectives

Educating healthcare professionals in patient safety is essential to achieving sustainable improvements in care. This study aimed to identify the key constituents of patient safety education alongside its facilitators and barriers from a frontline perspective.

Methods

An electronic survey was sent to 592 healthcare professionals and educators in patient safety education in the United Kingdom. Two independent reviewers conducted a thematic analysis of the free-text data. Themes focused on effective content, learning practices and facilitators and barriers to patient safety education.

Results

Of 592 individuals completing the survey, 545 (92%) submitted analyzable responses. Interrater reliability of coding was high with Cohen k value of 0.86. Participants endorsed experiential and interactive learning as ideal modalities for delivery and expressed a need for content to be based on real clinical cases and tailored to the needs of the learners. The most commonly mentioned facilitators were standardization of methods and assessment (49%), dedicated funding (21%), and culture of openness (20%). Staffing problems and high workload (41%) and lack of accessibility of training (23%) were identified as primary barriers of efficacy and uptake.

Conclusions

This study identified key factors to the success of patient safety education in terms of content and delivery alongside facilitators and barriers. Future curricula developers and interventions should improve standardization, funding, culture, and access so as to optimize education programs to enhance patient safety.
Defining the Epidemiology of Safety Risks in Neonatal Intensive Care Unit Patients Requiring Surgery
Authors: France Daniel J. , Slagle Jason , Schremp Emma , Moroz Sarah , Hatch L. Dupree , Grubb Peter , Vogus Timothy J. , Shotwell Matthew S. , Lorinc Amanda , Lehmann Christoph U. , Robinson Jamie , Crankshaw Marlee , Sullivan Maria , Newman Timothy A. , Wallace Tamara , Weinger Matthew B. , Blakely Martin L.
Published: March 2020

Objective

The aim of the study was to determine the incidence, type, severity, preventability, and contributing factors of nonroutine events (NREs)—events perceived by care providers or skilled observers as a deviations from optimal care based on the clinical situation—in the perioperative (i.e., preoperative, operative, and postoperative) care of surgical neonates in the neonatal intensive care unit and operating room.

Methods

A prospective observational study of noncardiac surgical neonates, who received preoperative and postoperative neonatal intensive care unit care, was conducted at an urban academic children’s hospital between November 1, 2016, and March 31, 2018. One hundred twenty-nine surgical cases in 109 neonates were observed. The incidence and description of NREs were collected via structured researcher-administered survey tool of involved clinicians. Primary measurements included clinicians’ ratings of NRE severity and contributory factors and trained research assistants’ ratings of preventability.

Results

One or more NREs were reported in 101 (78%) of 129 observed cases for 247 total NREs. Clinicians reported 2 (2) (median, interquartile range) NREs per NRE case with a maximum severity of 3 (1) (possible range = 1–5). Trained research assistants rated 47% of NREs as preventable and 11% as severe and preventable. The relative risks for National Surgical Quality Improvement Program – pediatric major morbidity and 30-day mortality were 1.17 (95% confidence interval = 0.92–1.48) and 1.04 (95% confidence interval = 1.00–1.08) in NRE cases versus non-NRE cases.

Conclusions

The incidence of NREs in neonatal perioperative care at an academic children’s hospital was high and of variable severity with a myriad of contributory factors.
Reported preexposure prophylaxis use among male sex partners of HIV-positive men: 2016–2018
Authors: Beer Linda , Tie Yunfeng , Smith Dawn K. , Fagan Jennifer L. , Shouse R. Luke
Published: March 2020

Objective:

To estimate the proportion of US HIV-positive men who report a male HIV-negative/unknown status (HIV-discordant) sexual partner taking preexposure prophylaxis (PrEP), and the use of multiple HIV prevention strategies within partnerships.

Design:

The Medical Monitoring Project is a complex sample survey of US adults with diagnosed HIV.

Methods:

We used data collected during June 2016 to May 2018 among sexually active HIV-positive men who had at least one HIV-discordant male partner (N = 1871) to estimate the weighted prevalence of reporting at least one partner taking PrEP. Among HIV-discordant partnerships (N = 4029), we estimated PrEP use, viral suppression among HIV-positive partners, and condomless anal sex. We evaluated significant (P < 0.05) differences between groups using prevalence ratios with predicted marginal means.

Results:

Twenty-eight percent of sexually active HIV-positive MSM reported at least one HIV-discordant male partner taking PrEP. Twenty percent of HIV-discordant partners were reported to be taking PrEP; 73% were taking PrEP or the HIV-positive partner was virally suppressed. PrEP use was lower among black and Hispanic partners compared with white partners (12% and 19% vs. 27%). Fewer black than white MSM were in partnerships in which PrEP was used or the HIV-positive partner had sustained viral suppression (69% vs. 77%). Condomless anal intercourse was more prevalent in partnerships involving PrEP use and in partnerships involving either PrEP use or sustained viral suppression among the HIV-positive partner.

Conclusion:

PrEP use was reported among one in five partners, with disparities between black and white partners. Increasing PrEP use and decreasing racial/ethnic disparities could reduce disparities in HIV incidence and help end the US HIV epidemic.
Virtual Noncontrast Images From Portal Venous Phase Spectral-Detector CT Acquisitions for Adrenal Lesion Characterization
Authors: Laukamp Kai Roman , Kessner Rivka , Halliburton Sandra , Zopfs David , Gupta Amit , Große Hokamp Nils
Published: March 2020

Objective

The aim of this study was to investigate if Hounsfield unit (HU) values from virtual noncontrast (VNC) images derived from portal venous phase spectral-detector computed tomography can help to differentiate adrenal adenomas and metastases.

Methods

Spectral-detector computed tomography datasets of 33 patients with presence of adrenal lesions and standard of reference for lesion origin by follow-up/prior examinations or dedicated magnetic resonance imaging were included. Conventional and VNC images were reconstructed from the same scan. Region of interest–based image analysis was performed in adrenal lesions and contralateral healthy adrenal tissue.

Results

The 33 lesions consisted of 23 adenomas and 10 metastases. Hounsfield unit values of all lesions in VNC images were significantly lower compared with conventional images (18.2 ± 12.6 HU vs 59.6 ± 21.7 HU, P < 0.001). Hounsfield unit values in adenomas were significantly lower in VNC images (11.3 ± 6.5 HU vs 34.1 ± 9.1 HU, P < 0.001).

Conclusions

Virtual noncontrast HU values differed significantly between adrenal adenomas and metastases and can therefore be used for improved characterization of incidental adrenal lesions and definition of adrenal adenomas.
Long-term Evaluation of Teres Major to Infraspinatus Transfer for Treatment of Shoulder Sequelae in Obstetrical Brachial Plexus Palsy
Authors: El-Gammal Tarek Abdalla , Ali Amr El-Sayed , Kotb Mohamed Mostafa , Saleh Waleed Riad , El-Gammal Yousif Tarek
Published: March 2020

Background

The long-term results of soft tissue rebalancing procedures of the shoulder in obstetric brachial plexus palsy have been scarcely reported. The effect of this procedure on the evolution of secondary bone changes has been a subject of controversy.

Methods

Twenty-six children are included in this study. All initially had postganglionic C5-6 or C5-7 (Narakas types I and II) obstetric brachial plexus palsy, which spontaneously recovered. Children included are those who had persistent external rotation weakness with or without internal rotation contracture, nondysplastic glenohumeral joint, and functioning teres major. All had anterior shoulder release and teres major to infraspinatus transfer to correct internal rotation deformity and/or increase active shoulder external rotation. Patients were 18 males and 8 females. The right upper limb was affected in 16 patients, and the left in 10. Surgery was performed at an average age of 3.01 years (range, 1–10 years). Follow-up averaged 8.2 years (range, 5–16 years). Eight cases (30%) were followed up for 10 years or greater. Age at final follow-up averaged 10.5 years (range, 6–17.8 years).

Results

The results showed to be significant: 67 degrees (63%), 71.3 degrees (412%), and −32 degrees (−35%), respectively. There was no single recurrence of internal rotation deformity. Global Mallet score averaged 20 ± 2.7. Global abduction and external rotation averaged 3.5 ± 0.8 and 4 ± 0.3, respectively. Shoulder abduction range included an average of 45 degrees glenohumeral and 65 degrees scapulothoracic motion. Postoperative internal rotation in adduction was limited to 55.96 ± 25.65 degrees and was significantly lower that the preoperative value. Radiological measurements showed no significant differences between the operated and normal sides.

Conclusions

We conclude that the long-term results after soft tissue rebalancing, combined with open reduction when required, demonstrated significant improvement of abduction and external rotation and significant loss of internal rotation. The difference in glenoid version and humeral head subluxation continued to be insignificant compared with the normal side.
Versatility of the Berger-Tenenhaus Approach for Mandibular Fractures
Authors: Thayer Jacob , Mailey Brian
Published: March 2020

Introduction:

Mandibular fractures between the angle and condyle can be difficult to access and treat. The authors sought to evaluate a small transcutaneous incision between the marginal mandibular and buccal nerve branches (Berger-Tenenhaus incision) to treat these fractures.

Methods:

Ten cadaveric hemi-faces were dissected. Surrounding facial nerve branches were identified and measured in relation to the discussed incision. Our clinical experience with the approach for mandibular angle, ramus, subcondylar, and condylar fractures was reviewed. Operative technique and postoperative outcomes were examined.

Results:

The incision is located in a safe interval between neighboring facial nerve branches. Marginal mandibular nerve branches maintained a consistent distance beneath the incision along its length (median distances of 0.95-cm (SD ± 0.5), 1.05-cm (SD ± 0.5), and 1.00-cm (SD ± 0.8) posterior to anterior, respectively). Buccal nerve branches increased in distance and ascended away from the incision line (median distances of 0.75-cm (SD ± 0.9), 1.4-cm (SD ± 0.8), and 1.45-cm (SD ± 0.9) respectively posterior to anterior). No nerves were injured. In our clinical experience, all postoperative patients (n = 9) have had successful fracture reduction with restoration of occlusion, intact facial nerve function and an acceptable cosmetic result.

Conclusions:

The Berger-Tenenhaus incision can safely and efficiently be used to treat difficult to access mandible fractures between the angle and condyle.

Level of Evidence:

VI.
Syngnathia in Spectrum of Oromandibular Limb Hypogenesis Syndrome
Authors: Máximo Geiza , Silva Mayara Branco , Antonio Maria Ângela R.G.M , do Monte Thais Miguel , Raposo-Amaral Cesar Augusto , Raposo-Amaral Cassio Eduardo
Published: March 2020

Syngnathia is a rare facial anomaly associated with neonatal problems, including a compromised airway, and the inability to take in solids and/or liquids. Syngnathia is included within the spectrum of oromandibular limb hypogenesis syndrome, an extremely rare condition characterized by varying degrees of congenital malformation involving the tongue, mandible, and limbs. In this report, we describe the case of a 41-day-old Caucasian female infant who was unable to open her mouth beginning at birth. The authors performed osteotomies to separate fused bone, and placed a bite block at the osteotomy sites to prevent bone fusion recurrence. At 2 years of follow-up patient remained with 14 mm of mouth opening.
The Effectiveness of Simulation-Based Team Training in Obstetrics Emergencies for Improving Technical Skills
Authors: Yucel Cigdem , Hawley Glenda , Terzioglu Fusun , Bogossian Fiona
Published: March 2020

Summary Statement

This review explores the effectiveness of simulation-based team training in obstetric emergencies for improving technical skills. A literature search was conducted that included all articles to January 2018. A total of 21 articles were included from a potential 1327 articles. Each included study was assessed for impact of the training program using Kirkpatrick's 4-level model. Only the performance of technical skills was evaluated.

Five studies reported on acceptance of simulation as an education tool at a level 1. Level 2 outcomes were reported in 7 studies where staff demonstrated improved skills in an educational setting. Three studies reported improved performance in a clinical setting at a level 3. Ten studies were categorized as level 4 and found that simulation learning was translated into improved techniques or maneuvers in reduced time frames in emergency situations of shoulder dystocia and postpartum hemorrhage. There was evidence that neonatal outcomes were improved.
Valproic acid induces nuclear factor erythroid 2-related factor 2 expression in fetal and neonatal brains but not in adult brain: evidence of the gamma-aminobutyric acid-shift hypothesis
Authors: Gifford Janace J. , Norton Sara A. , Kusnecov Alexander W. , Wagner George C.
Published: March 2020

The gamma-aminobutyric acid (GABA)-shift hypothesis proposes that GABA agonist action is excitatory early in development and transitions to an inhibitory role later in life. In experiment 1, the nonspecific GABA agonist, valproic acid (VPA), was administered to pregnant C57BL/6 mice on embryonic day 13. Fetal and maternal brains were harvested 2 h post-VPA exposure and assayed for nuclear factor erythroid 2-related factor 2 (NRF2) and H3 expression through western blot analysis. In experiment 2, VPA was administered to neonatal pups on P14 and adult mice on P60. In both experiments, it was observed that NRF2 expression was increased in fetal and neonatal brains, but not in the adult brain. Because NRF2 expression is activated by oxidative stress, these results imply support of the GABA-shift hypothesis in that VPA may exert its developmental damage in the fetal and neonatal periods through excitotoxicity.
Convulsive responses to seizure-inducible drugs are exacerbated in progranulin-deficient mice
Authors: Kuroda Machi , Matsuwaki Takashi , Tanaka Yoshinori , Yamanouchi Keitaro , Nishihara Masugi
Published: March 2020

Progranulin (PGRN) is a glycoprotein that is widely expressed among organs, including the central nervous system. PGRN insufficiency is involved in various neurodegenerative disorders such as frontotemporal dementia, Alzheimer’s disease, and neuronal ceroid lipofuscinosis. One of the major causes of neuronal damage is hyperactivation of the cerebrum triggered by upregulation of excitatory systems. In the present study, we examined the possible involvement of PGRN in modulating excitability of the cerebrum using wild type and PGRN-deficient mice. First, we treated wild type and PGRN-deficient mice with seizure-inducible drugs, bicuculline orN-methyl-D-aspartate (NMDA), which provoke hyperexcitement of neurons. PGRN-deficient mice showed higher intensity of seizure and longer duration of convulsive behavior when treated with either bicuculline or NMDA. Next, we quantified the expression of NMDA receptor subunits in the hippocampus and cerebral cortex. The expression level of NR2A subunit protein was significantly higher in the hippocampus of PGRN-deficient mice, while no difference was observed in the cerebral cortex. On the other hand, mRNA levels of NMDA receptor subunits in the hippocampus were comparable or even lower in PGRN-deficient mice. These results suggest that PGRN modulates the excitability of the cerebrum by regulating at least partially the protein level of NMDA receptors in the hippocampus.
Endurance exercise-induced expression of autophagy-related protein coincides with anabolic expression and neurogenesis in the hippocampus of the mouse brain
Authors: Jang Yongchul
Published: March 2020

Autophagy and neurogenesis play a pivotal role in maintaining cellular homeostasis of neurons in the brain. Endurance exercise (EXE) serves as a potent regulator of both autophagy and neurogenesis in the hippocampus of the brain; however, the underlying molecular mechanisms of the dual expression remains unclear. Thus, we examined the signaling pathways of EXE-induced autophagy and neurogenesis-associated protein expression in the hippocampus. C57BL/6 male mice (10 weeks old) were randomly divided into two groups: control group (n = 10) and EXE group (EXE, n = 10). Our results showed that EXE increased expression of autophagy-related protein [LC3 II, BECLIN1, autophagy-related 7 (ATG7), p62, LAMP2, CATHEPSIN L and transcription factor EB] in the presence of anabolic signaling expression (AKT–mammalian target of rapamycin–ribosomal S6 kinase). Intriguingly, long-term EXE-mediated neurogenesis in the hippocampus was observed despite the downregulated expressions of canonical neurotrophic factors (e.g. brain-derived neurotrophic factor, glial cell line-derived neurotrophic factors and nerve growth factor); instead, upregulation of neuregulin-1 (NRG1)-mediated signaling cascades (e.g. NRG1-extracellular signal-regulated kinase–ribosomal s6 kinase–cyclic adenosine mono-phosphate response element-binding protein) were associated with EXE-induced hippocampal neurogenesis and synaptic plasticity. Our data, for the first time, show that EXE-mediated expression of autophagy-related protein coincides with anabolic expression and that NRG1 is involved in EXE-mediated neurogenesis and synaptic plasticity. Taken together, this study provides a novel mechanism of hippocampal autophagy and neurogenesis, which may provide potential insight into developing therapeutic neuroprotective strategies.
Age specificity of cases and attack rate of novel coronavirus disease (COVID-19)
Authors: Mizumoto Kenji , Omori Ryosuke , Nishiura Hiroshi
Published: March 2020

Age distribution of the cases with novel coronavirus disease (COVID-19) is rather different from that of influenza. In China, there were few reported cases among children [1] and serious or fatal child cases were also very infrequent. The age specificity is particularly important in designing details of social distancing, including school closure, as interventions, which is now recognized as the mainstream of interventions against COVID-19. Investigating the details of contacts, substantial susceptibility among children was demonstrated [2], but further insights into underlying mechanisms should be explored. Here we examined the age distribution of COVID-19 cases in Japan from January to March, 2020.
Lessons drawn from China and South Korea for managing COVID-19 epidemic: insights from a comparative modeling study
Authors: Tang Biao , Xia Fan , Bragazzi Nicola Luigi , Wang Xia , He Sha , Sun Xiaodan , Tang Sanyi , Xiao Yanni , Wu Jianhong
Published: March 2020

We conducted a comparative study of COVID-19 epidemic in three different settings: mainland China, the Guangdong province of China and South Korea, by formulating two disease transmission dynamics models incorporating epidemic characteristics and setting-specific interventions, and fitting the models to multi-source data to identify initial and effective reproduction numbers and evaluate effectiveness of interventions. We estimated the initial basic reproduction number for South Korea, the Guangdong province and mainland China as 2.6 (95% confidence interval (CI): (2.5, 2.7)), 3.0 (95%CI: (2.6, 3.3)) and 3.8 (95%CI: (3.5,4.2)), respectively, given a serial interval with mean of 5 days with standard deviation of 3 days. We found that the effective reproduction number for the Guangdong province and mainland China has fallen below the threshold 1 since February 8th and 18th respectively, while the effective reproduction number for South Korea remains high, suggesting that the interventions implemented need to be enhanced in order to halt further infections. We also project the epidemic trend in South Korea under different scenarios where a portion or the entirety of the integrated package of interventions in China is used. We show that a coherent and integrated approach with stringent public health interventions is the key to the success of containing the epidemic in China and specially its provinces outside its epicenter, and we show that this approach can also be effective to mitigate the burden of the COVID-19 epidemic in South Korea. The experience of outbreak control in mainland China should be a guiding reference for the rest of the world including South Korea.
Virus strain of a mild COVID-19 patient in Hangzhou represents a new trend in SARS-CoV-2 evolution related to Furin cleavage site
Authors: Jin Xi , Xu Kangli , Jiang Penglei , Lian Jiangshan , Hao Shaorui , Yao Hangping , Jia Hongyu , Zhang Yimin , Zheng Lin , zheng Nuoheng , Chen Dong , Yao Jinmei , Hu Jianhua , Gao Jianguo , Wen Liang , Shen Jian , Ren Yue , Yu Guodong , Wang Xiaoyan , Lu Yingfeng , Yu Xiaopeng , Yu Liang , Xiang Dairong , Wu Nanping , Lu Xiangyun , Cheng Linfang , Liu Fumin , Wu Haibo , Jin Changzhong , Yang Xiaofeng , Qian Pengxu , Qiu Yunqing , Sheng Jifang , Liang Tingbo , Li Lanjuan , Yang Yida
Published: March 2020

The outbreak of COVID-19 become enormous threat to human beings, showing unclear virus mutation during dissemination. We found, in our 788 confirmed COVID-19 patients, the decreased rate of severe/critical type, increased liver/kidney damage and prolonged period of nuclear acid positivity, when compared with Wuhan. To investigate underlining mechanisms, we isolated one strain of SARS-CoV-2 (ZJ01) in mild COVID-19 patient and found the existence of 35 specific gene mutation by gene alignment. Further phylogenetic analysis and RSCU heat map results suggested that ZJ01 may be a potential evolutionary branch of SARS-CoV-2. We classified 54 strains of viruses worldwide (C/T type) based on the base (C or T) at positions 8824 and 28247. ZJ01 has both T at those sites, becoming the only TT type currently identified in the world. The prediction of Furin cleavage site (FCS) and the sequence alignment of virus family indicated that FCS may be an important site of coronavirus evolution. ZJ01 had mutations near FCS (F1-2), which caused changes in the structure and electrostatic distribution of S protein surface, further affecting the binding capacity of Furin. Single cell sequencing and ACE2-Furin co-expression results confirmed that Furin level was higher in the whole body, especially in glands, liver, kidney and colon while FCS may help SARS-CoV-2 infect these organs. The evolutionary pattern of SARS-CoV-2 towards FCS formation may result in its clinical symptom becoming closer to HKU-1 and OC43 (the source of FCS sequence-PRRA) caused influenza, further showing potential in differentiating into mild COVID-19 subtypes.
Optimization of an Experimental Vaccine to PreventEscherichia coliUrinary Tract Infection
Authors: Forsyth Valerie S. , Himpsl Stephanie D. , Smith Sara N. , Sarkissian Christina A. , Mike Laura A. , Stocki Jolie A. , Sintsova Anna , Alteri Christopher J. , Mobley Harry L.T.
Published: March 2020

Urinary tract infections (UTI) affect half of all women at least once during their lifetime. The rise in extended-spectrum beta-lactamase-producing strains and potential for carbapenem resistance within uropathogenicEscherichia coli(UPEC), the most common causative agent of UTIs, creates an urgent need for vaccine development. Intranasal immunization of mice with UPEC outer membrane iron receptors, FyuA, Hma, IreA, or IutA, conjugated to cholera toxin, provides protection in the bladder or kidneys when challenged with UPEC CFT073 or 536. Based on these data, we sought to optimize the vaccination route (intramuscular, intranasal, or subcutaneous) in combination with adjuvants suitable for human use including alum, monophosphoryl lipid A (MPLA), unmethylated CpG synthetic oligodeoxynucleotides (CpG), polyinosinic:polycytodylic acid (polyIC), and mutated heat-labileE. colienterotoxin (dmLT). Mice intranasally vaccinated with dmLT-IutA or dmLT-Hma displayed a significant reduction in bladder colonization (86-fold and 32-fold, respectively) with 40–42% of mice having no detectable colony forming units (CFU). Intranasal vaccination of mice with CpG-IutA and polyIC-IutA significantly reduced kidney colonization (131-fold) and urine CFU (22-fold), respectively. dmLT generated the most consistently robust antibody response in intranasally immunized mice, while MPLA and alum produced greater concentrations of antigen-specific serum IgG with intramuscular immunization. Based on these results, we conclude that intranasal administration of Hma or IutA formulated with dmLT adjuvant provides the greatest protection from UPEC UTI. This study advances our progress toward a vaccine against uncomplicated UTI, which will significantly improve the quality of life for women burdened by recurrent UTI and enable better antibiotic stewardship.

Importance

Urinary tract infections (UTI) are among the most common bacterial infection in humans, affecting half of all women at least once during their lifetimes. The rise in antibiotic resistance and health care costs emphasizes the need to develop a vaccine against the most common UTI pathogen,Escherichia coli.Vaccinating mice intranasally with a detoxified heat-labile enterotoxin and two surface exposed receptors, Hma or IutA, significantly reduced bacterial burden in the bladder. This work highlights progress in the development of a UTI vaccine formulated with adjuvants suitable for human use and antigens that encode outer membrane iron receptors required for infection in the iron-limited urinary tract.
Estimation of instant case fatality rate of COVID-19 in Wuhan and Hubei based on daily case notification data
Authors: Cao Lei , Huang Ting-ting , Zhang Jun-xia , Qin Qi , Liu Si-yu , Xue Hui-min , Gong Ya-xin , Ning Chang-hua , Shen Xiao-tong , Yang Jia-xin , Mi Yan-ni , Xiao Xue , Cao Yong-xiao
Published: March 2020

Background

The outbreak of coronavirus disease 2019 (COVID-19) initially appeared and has most rapidly spread in Wuhan, China. The case fatality rate is the most direct indicator to assess the hazards of an infectious disease. We aimed to estimate the instant fatality rate and cure rate of COVID-19 in Wuhan City and its affiliated Hubei Province.

Methods

We collected the daily case notification data of COVID-19 from Dec 8, 2019 to Mar 10, 2020 in Wuhan City and Hubei Province officially announced by the Chinese authority. The numbers of daily confirmed/deaths/cured cases and the numbers of daily cumulative confirmed/deaths/cured cases were obtained. The death time and cure time of COVID-19 patients were calculated based on the dates of diagnosis, death and discharge of individual cases. Then the estimated diagnosis dates of deaths and cured cases were obtained on the basis of the median death or medium cure time, respectively. Finally, the instant fatality rate of COVID-19 was calculated according to the numbers of deaths and cured cases on the same estimated diagnosis dates.

Results

From Jan 1, 2020 to Feb 22, 2020 in Wuhan City, the instant case fatality rate of COVID-19 was 3.4%∼19.5% and the instant cured rate was 80.0%∼96.6%. The average fatality rate reached 11.4% while the average cure rate was 88.6%. During the same period in Hubei Province, the instant case fatality rate was 3.8%∼16.6% and the instant cured rate was 83.4%∼96.6%. The average fatality rate and the average cure rate were 9.2% and 91.8%, respectively.

Conclusions

The fatality rate and cure rate of COVID-19 in Wuhan City and Hubei Province were underestimated. Wuhan showed higher fatality rate and cure rate than the whole Hubei Province did.
A modeling framework for adaptive lifelong learning with transfer and savings through gating in the prefrontal cortex
Authors: Tsuda Ben , Tye Kay M. , Siegelmann Hava T. , Sejnowski Terrence J.
Published: March 2020

The prefrontal cortex encodes and stores numerous, often disparate, schemas and flexibly switches between them. Recent research on artificial neural networks trained by reinforcement learning has made it possible to model fundamental processes underlying schema encoding and storage. Yet how the brain is able to create new schemas while preserving and utilizing old schemas remains unclear. Here we propose a simple neural network framework based on a modification of the mixture of experts architecture to model the prefrontal cortex’s ability to flexibly encode and use multiple disparate schemas. We show how incorporation of gating naturally leads to transfer learning and robust memory savings. We then show how phenotypic impairments observed in patients with prefrontal damage are mimicked by lesions of our network. Our architecture, which we call DynaMoE, provides a fundamental framework for how the prefrontal cortex may handle the abundance of schemas necessary to navigate the real world.
A data-driven drug repositioning framework discovered a potential therapeutic agent targeting COVID-19
Authors: Ge Yiyue , Tian Tingzhong , Huang Suling , Wan Fangping , Li Jingxin , Li Shuya , Yang Hui , Hong Lixiang , Wu Nian , Yuan Enming , Cheng Lili , Lei Yipin , Shu Hantao , Feng Xiaolong , Jiang Ziyuan , Chi Ying , Guo Xiling , Cui Lunbiao , Xiao Liang , Li Zeng , Yang Chunhao , Miao Zehong , Tang Haidong , Chen Ligong , Zeng Hainian , Zhao Dan , Zhu Fengcai , Shen Xiaokun , Zeng Jianyang
Published: March 2020

The global spread of SARS-CoV-2 requires an urgent need to find effective therapeutics for the treatment of COVID-19. We developed a data-driven drug repositioning framework, which applies both machine learning and statistical analysis approaches to systematically integrate and mine large-scale knowledge graph, literature and transcriptome data to discover the potential drug candidates against SARS-CoV-2. The retrospective study using the past SARS-CoV and MERS-CoV data demonstrated that our machine learning based method can successfully predict effective drug candidates against a specific coronavirus. Ourin silicoscreening followed by wet-lab validation indicated that a poly-ADP-ribose polymerase 1 (PARP1) inhibitor, CVL218, currently in Phase I clinical trial, may be repurposed to treat COVID-19. Ourin vitroassays revealed that CVL218 can exhibit effective inhibitory activity against SARS-CoV-2 replication without obvious cytopathic effect. In addition, we showed that CVL218 is able to suppress the CpG-induced IL-6 production in peripheral blood mononuclear cells, suggesting that it may also have anti-inflammatory effect that is highly relevant to the prevention immunopathology induced by SARS-CoV-2 infection. Further pharmacokinetic and toxicokinetic evaluation in rats and monkeys showed a high concentration of CVL218 in lung and observed no apparent signs of toxicity, indicating the appealing potential of this drug for the treatment of the pneumonia caused by SARS-CoV-2 infection. Moreover, molecular docking simulation suggested that CVL218 may bind to the N-terminal domain of nucleocapsid (N) protein of SARS-CoV-2, providing a possible model to explain its antiviral action. We also proposed several possible mechanisms to explain the antiviral activities of PARP1 inhibitors against SARS-CoV-2, based on the data present in this study and previous evidences reported in the literature. In summary, the PARP1 inhibitor CVL218 discovered by our data-driven drug repositioning framework can serve as a potential therapeutic agent for the treatment of COVID-19.
Antibiotic hypersensitivity signatures identify targets for attack in theAcinetobacter baumanniicell envelope
Authors: Geisinger Edward , Mortman Nadav J. , Dai Yunfei , Cokol Murat , Syal Sapna , Farinha Andrew , Fisher Delaney , Tang Amy , Lazinski David , Wood Stephen , Anthony Jon , van Opijnen Tim , Isberg Ralph R.
Published: March 2020

Acinetobacter baumanniiis an opportunistic pathogen that is a critical, high-priority target for new antibiotic development. Clearing ofA. baumanniirequires relatively high doses of antibiotics across the spectrum, primarily due to its protective cell envelope. Many of the proteins that support envelope integrity and modulate drug action are uncharacterized, largely because there is an absence of orthologs for several proteins that perform essential envelope-associated processes, impeding progress on this front. To identify targets that can synergize with current antibiotics, we performed an exhaustive analysis ofA. baumanniimutants causing hypersensitivity to a multitude of antibiotic treatments. By examining mutants with antibiotic hypersensitivity profiles that parallel mutations in proteins of known function, we show that the function of poorly annotated proteins can be predicted and used to identify candidate missing link proteins in essentialA. baumanniiprocesses. Using this strategy, we uncovered multiple uncharacterized proteins with critical roles in cell division or cell elongation, and revealed that a predicted cell wall D,D-endopeptidase has an unappreciated function in lipooligosaccharide synthesis. Moreover, we provide a genetic strategy that uses hypersensitivity signatures to predict drug synergies, allowing the identification of β-lactams that work cooperatively based on the cell wall assembly machineries that they preferentially target. These data reveal multiple pathways critical for envelope growth inA. baumanniithat can be targeted in combination strategies for attacking the pathogen.
A human monoclonal antibody blocking SARS-CoV-2 infection
Authors: Wang Chunyan , Li Wentao , Drabek Dubravka , Okba Nisreen M.A. , van Haperen Rien , Osterhaus Albert D.M.E. , van Kuppeveld Frank J.M. , Haagmans Bart L. , Grosveld Frank , Bosch Berend-Jan
Published: March 2020

The emergence of the novel human coronavirus SARS-CoV-2 in Wuhan, China has caused a worldwide epidemic of respiratory disease (COVID-19). Vaccines and targeted therapeutics for treatment of this disease are currently lacking. Here we report a human monoclonal antibody that neutralizes SARS-CoV-2 (and SARS-CoV). This cross-neutralizing antibody targets a communal epitope on these viruses and offers potential for prevention and treatment of COVID-19.
Drivers of change in the realised climatic niche of terrestrial mammal species
Authors: Moreno Di Marco , Pacifici Michela , Maiorano Luigi , Rondinini Carlo
Published: March 2020

The breadth of a species’ climatic niche is an important ecological trait that allows adaptation to climate change, but human activities drive niche erosion. Life-history traits, such as dispersal ability and reproductive speed, instead allow species to cope with climate change. But how do these characteristics act in combination with human pressure to determine niche change? Here we investigate the patterns and drivers of change in the realised climatic niche of 589 terrestrial mammal species. Our goal is to disentangle the impacts of humans, climate change, and life history. We calibrated the past and present climatic niches of each species by considering past climatic conditions (Mid Holocene) within their pre-human impact distributions, and current climatic conditions within the current distributions. Depending on the relationship between past and current niche, we defined four categories of change: “shrink”, “shift”, “stable”, and “expand”. We found over half of the species in our sample have undergone niche shrink, while only 15-18% of species retained a stable niche. After controlling for biogeography, climatic factors were the strongest correlates of species niche change, followed by anthropogenic pressure and species’ life history. Factors that increased the probability of niche shrink include: overall climatic instability in the area (both intermediate or high), large body mass, long gestation time, highly carnivorous or herbivorous diets, historical land-use change, and current human population density. We identified the conditions under which species are less likely to maintain their niche breadth, potentially losing adaptation capacity under climate change. Species with these characteristics require interventions that facilitate natural dispersal or assisted colonisation, to survive to rapidly changing climates.
A new form of actin assembly around theShigella-containing vacuole regulates its intracellular niche
Authors: Kühn Sonja , Bergqvist John , Barrio Laura , Lebreton Stephanie , Zurzolo Chiara , Enninga Jost
Published: March 2020

The enteroinvasive bacteriumShigella flexneriforces its uptake into non-phagocytic host cells through the translocation of T3SS effectors that subvert the actin cytoskeleton. Here, we reportde novoactin polymerization after cellular entry around the bacterial containing vacuole (BCV) leading to the formation of a dynamic actin cocoon. This cocoon is thicker than any described cellular actin structure and functions as a gatekeeper for the cytosolic access of the pathogen. Host Cdc42, Toca-1, N-WASP, WIP, the Arp2/3 complex, cortactin, coronin, and cofilin are recruited to the actin cocoon. They are subverted by T3SS effectors, such as IpgD, IpgB1, and IcsB. IcsB immobilizes components of the actin polymerization machinery at the BCV. This represents a novel microbial subversion strategy through localized entrapment of host actin regulators causing massive actin assembly. We propose that the cocoon protectsShigella’s niche from canonical maturation or host recognition.
Multiple Sex-Specific Differences in the Regulation of Meiotic Progression inC. elegans
Authors: Fielder Sara M. , Kempfer Rieke , Kelly William G.
Published: March 2020

Meiosis is a highly conserved sexual process, yet significant differences exist between males and females in meiotic regulation in many species. Meiotic progression in C. elegans males proceeds more rapidly than female meiosis, suggesting that female meiotic regulation may be more stringent than in males. We have identified multiple differences in the regulation of synapsis, including a difference that suggests the presence of a female-specific meiotic checkpoint that senses the proper initiation of synapsis. This checkpoint is detected by sex differences in the targeting of histone H3 lysine 9 dimethylation (H3K9me2) to unsynapsed chromatin. During oogenic meiosis in hermaphrodites, the failure to initiate synapsis leads to failure to target H3K9me2 enrichment on unsynapsed chromosomes. Loss of the pachytene checkpoint does not reintroduce H3K9me2 enrichment in hermaphrodites, indicating these checkpoints are separable. In contrast, widespread H3K9me2 enrichment occurs as a result of loss of synapsis initiation in both male meiosis and during spermatogenic meiosis in larval XX hermaphrodites. Additionally, male synapsis is insensitive to loss of the dynein motor light chain DLC-1 and to elevated temperatures, whereas female synapsis is prevented by both conditions. We also show that loss of spindle assembly checkpoint proteins, which provide a kinetic barrier to meiotic progression and are required for DLC-1-dependent synapsis phenotypes in hermaphrodites, does not speed up the rate of synapsis in spermatogenic meiosis. These results indicate that meiosis proceeds more rapidly in males because males lack barriers to meiotic progression that are activated by defective synapsis initiation in females.
(E)-6-(Furan-2-ylmethylidene)-6,7,8,9-tetrahydropyrido[2,1-b]quinazoline-11-thione
Authors: Tojiboev Akmal , Nasrullaev Azizbek , Turgunov Kambarali , Elmuradov Burkhan , Tashkhodjaev Bakhodir
Published: March 2020

A quinazolinthione, C17H14N2OS, was synthesized by the condensation reaction of 6,7,8,9-tetrahydro-11H-pyrido[2,1-b]quinazolin-11-thione with furfural. The molecule crystallizes in the monoclinic system (Ccspace group) and has anEconfiguration with respect to the exocyclic C=C bond. In the crystal, molecules are linked through C—H...π(furan) interactions, forming zigzag chains propagating along the [001] direction.
Impact of ASX corporate governance guidelines on sustainability reporting
Authors: Czernkowski Robert , Kean Stephen , Lim Stephen
Published: March 2020

Purpose

This paper aims to examine the impact of the Australian Securities Exchange Corporate Governance recommendations on the breadth (amount of items covered) of (environmental and social) sustainability reporting by the firms in the Top 100, around the change from G3.1 to G4 disclosure regimes.

Design/methodology/approach

This paper undertakes comparisons of means and regression models to investigate the changes between disclosure scores of 98 listed entities from the 2013 G3.1 to the 2015 G4 disclosure regimes.

Findings

This paper finds that average disclosure levels did not change. Nonetheless, disclosure practices did vary by entity size and performance. Analysis of 2015 disclosures contingent on 2013 disclosure practice indicates that disclosure changes are consistent with a pattern of mean reversion.

Practical implications

Evidence that low disclosers increased disclosure and high disclosers reduced disclosers is consistent with the idea that sustainability disclosure is not so much driven by any ethical considerations, but rather by a desire to not be a disclosure outlier. Reliance on voluntary disclosure to achieve a socially desired level of disclosure is unlikely to bear fruit.

Originality/value

This paper contributes to the literature on sustainability by examining firm responses to change in disclosure regimes, and concluding that size and peer relativities drive the disclosure process.