bluuebunny/crossref_metadata_2025 huggingface dataset:
Correction to: Effects of robot-assisted gait training in patients with Parkinson’s disease: study protocol for a randomized controlled trial
Authors: Kang Min-Gu , Yun Seo Jung , Shin Hyun Iee , Kim Eunkyung , Lee Hyun Haeng , Oh Byung-Mo , Seo Han Gil
Published: May 2020

An amendment to this paper has been published and can be accessed via the original article.
Single-cell RNA sequencing reveals the tumor microenvironment and facilitates strategic choices to circumvent treatment failure in a chemorefractory bladder cancer patient
Authors: Lee Hye Won , Chung Woosung , Lee Hae-Ock , Jeong Da Eun , Jo Areum , Lim Joung Eun , Hong Jeong Hee , Nam Do-Hyun , Jeong Byong Chang , Park Se Hoon , Joo Kyeung-Min , Park Woong-Yang
Published: May 2020

Background

Tumor cell-intrinsic mechanisms and complex interactions with the tumor microenvironment contribute to therapeutic failure via tumor evolution. It may be possible to overcome treatment resistance by developing a personalized approach against relapsing cancers based on a comprehensive analysis of cell type-specific transcriptomic changes over the clinical course of the disease using single-cell RNA sequencing (scRNA-seq).

Methods

Here, we used scRNA-seq to depict the tumor landscape of a single case of chemo-resistant metastatic, muscle-invasive urothelial bladder cancer (MIUBC) addicted to an activating Harvey rat sarcoma viral oncogene homolog (HRAS) mutation. In order to analyze tumor evolution and microenvironmental changes upon treatment, we also applied scRNA-seq to the corresponding patient-derived xenograft (PDX) before and after treatment with tipifarnib, a HRAS-targeting agent under clinical evaluation.

Results

In the parallel analysis of the human MIUBC and the PDX, diverse stromal and immune cell populations recapitulated the cellular composition in the human and mouse tumor microenvironment. Treatment with tipifarnib showed dramatic anticancer effects but was unable to achieve a complete response. Importantly, the comparative scRNA-seq analysis between pre- and post-tipifarnib-treated PDX revealed the nature of tipifarnib-refractory tumor cells and the tumor-supporting microenvironment. Based on the upregulation of programmed death-ligand 1 (PD-L1) in surviving tumor cells, and the accumulation of multiple immune-suppressive subsets from post-tipifarnib-treated PDX, a PD-L1 inhibitor, atezolizumab, was clinically applied; this resulted in a favorable response from the patient with acquired resistance to tipifarnib.

Conclusion

We presented a single case report demonstrating the power of scRNA-seq for visualizing the tumor microenvironment and identifying molecular and cellular therapeutic targets in a treatment-refractory cancer patient.
The rate and spectrum of mosaic mutations during embryogenesis revealed by RNA sequencing of 49 tissues
Authors: Muyas Francesc , Zapata Luis , Guigó Roderic , Ossowski Stephan
Published: May 2020

Background

Mosaic mutations acquired during early embryogenesis can lead to severe early-onset genetic disorders and cancer predisposition, but are often undetectable in blood samples. The rate and mutational spectrum of embryonic mosaic mutations (EMMs) have only been studied in few tissues, and their contribution to genetic disorders is unknown. Therefore, we investigated how frequent mosaic mutations occur during embryogenesis across all germ layers and tissues.

Methods

Mosaic mutation detection in 49 normal tissues from 570 individuals (Genotype-Tissue Expression (GTEx) cohort) was performed using a newly developed multi-tissue, multi-individual variant calling approach for RNA-seq data. Our method allows for reliable identification of EMMs and the developmental stage during which they appeared.

Results

The analysis of EMMs in 570 individuals revealed that newborns on average harbor 0.5–1 EMMs in the exome affecting multiple organs (1.3230 × 10−8 per nucleotide per individual), a similar frequency as reported for germline de novo mutations. Our multi-tissue, multi-individual study design allowed us to distinguish mosaic mutations acquired during different stages of embryogenesis and adult life, as well as to provide insights into the rate and spectrum of mosaic mutations. We observed that EMMs are dominated by a mutational signature associated with spontaneous deamination of methylated cytosines and the number of cell divisions. After birth, cells continue to accumulate somatic mutations, which can lead to the development of cancer. Investigation of the mutational spectrum of the gastrointestinal tract revealed a mutational pattern associated with the food-borne carcinogen aflatoxin, a signature that has so far only been reported in liver cancer.

Conclusions

In summary, our multi-tissue, multi-individual study reveals a surprisingly high number of embryonic mosaic mutations in coding regions, implying novel hypotheses and diagnostic procedures for investigating genetic causes of disease and cancer predisposition.
Therapeutic abortion in Iran: an epidemiologic study of legal abortion in 2 years
Authors: Mahdavi Seyed Amirhosein , Jafari Asieh , Azimi Khadijeh , Dehghanizadeh Nikoo , Barzegar Abdolrazagh
Published: May 2020

Objectives

Unsafe abortion is one of the most important causes of death and disability among mothers in countries where abortion is illegal. These conditions have changed since then. The present study has investigated the cases who were referred to the legal medicine organization to receive abortion permission. This country level secondary patient data analysis, investigated all the cases who were referred to the legal medicine centers of Iran for abortion permission during 2015 to 2017.

Results

From 21,477 applicants, 15,617 (72.71%) received permission including 14,367 (91.99%) for fetal abnormalities and 1250 (8.01%) for maternal diseases. The most common fetal abnormalities/disorders were nervous system malformations (26.4%), chromosomal abnormalities (18.4%) and of maternal diseases were circulatory system diseases (43.9%), neoplasms (13.4%) and genitourinary system diseases (9.9%). The most common reasons for not permission were lack of supplementary documents to prove (38.8%), not competency with the criteria (33.9%), and gestational age of more than 19 weeks (25.8%).
Expression patterns of SLIT/ROBO mRNAs reveal a characteristic feature in the entorhinal-hippocampal area of macaque monkeys
Authors: Sasaki Tetsuya , Komatsu Yusuke , Yamamori Tetsuo
Published: May 2020

Objective

SLITs are secreted glycoproteins that bind to Roundabouts (ROBOs) which are a family member of transmembrane receptors. SLIT signaling has well-conserved roles in mediating axon repulsion in a developing nervous system. We previously reported that SLIT1 mRNA is enriched in middle layers of the prefrontal cortex of macaque monkeys in a developmentally regulated manner. Other SLIT (SLIT2 and SLIT3) mRNAs showed preferential expressions in the prefrontal cortex with a distinct laminar pattern. To obtain further clues to the role of SLIT signaling in the organization of the primate brain, we performed ISH analysis of SLIT and ROBO mRNAs using adult macaque brain tissues.

Results

In this study, we examined the expression patterns of SLITs and ROBOs (ROBO1 and ROBO2) in other brain regions, and found intense and characteristic expression patterns of these genes in the entorhinal-hippocampal area. In situ hybridization analysis revealed that SLIT1 and SLIT2 mRNAs showed marked complementary distribution in the entorhinal cortex. SLIT and ROBO mRNAs were widely expressed in the hippocampus with modest regional preference. These findings suggest that each SLIT gene has a specialized role that is particularly important for prefrontal as well as hippocampal connectivity in the primate cortex.
Co-occurrence between C1 esterase inhibitor deficiency and autoimmune disease: a systematic literature review
Authors: Levy Donald , Craig Timothy , Keith Paul K. , Krishnarajah Girishanthy , Beckerman Rachel , Prusty Subhransu
Published: May 2020

Background

Hereditary angioedema (HAE) is caused by a SERPING1 gene defect resulting in decreased (Type I) or dysfunctional (Type II) C1 esterase inhibitor (C1-INH). The prevalence of autoimmune diseases (ADs) in patients with HAE appears to be higher than the general population. A systematic literature review was conducted to examine the co-occurrence between HAE and ADs.

Methods

PubMed/EMBASE were searched for English-language reviews, case reports, observational studies, retrospective studies, and randomized controlled trials up to 04/15/2018 (04/15/2015-04/15/2018 for EMBASE) that mentioned patients with HAE Type I or II and comorbid ADs. Non-human or in vitro studies and publications of C1-INH deficiency secondary to lymphoproliferative disorders or angiotensin-converting-enzyme inhibitors were excluded.

Results

Of the 2880 records screened, 76 met the eligibility criteria and 155 individual occurrences of co-occurring HAE and AD were mentioned. The most common ADs were systemic lupus erythematosus (30 mentions), thyroid disease (21 mentions), and glomerulonephritis (16 mentions). When ADs were grouped by MedDRA v21.0 High Level Terms, the most common were: Lupus Erythematosus and Associated Conditions, n = 52; Endocrine Autoimmune Disorders, n = 21; Gastrointestinal Inflammatory Conditions, n = 16; Glomerulonephritis and Nephrotic Syndrome, n = 16; Rheumatoid Arthritis and Associated Conditions, n = 11; Eye, Salivary Gland and Connective Tissue Disorders, n = 10; and Immune and Associated Conditions Not Elsewhere Classified, n = 5.

Conclusions

Based on literature reports, systemic lupus erythematosus is the most common AD co-occurring with HAE Type I and II. Cause and effect for co-occurring HAE and AD has not been clinically established but could be related to lack of sufficient C1-INH function.
Identification of amygdala-expressed genes associated with autism spectrum disorder
Authors: Herrero Maria Jesus , Velmeshev Dmitry , Hernandez-Pineda David , Sethi Saarthak , Sorrells Shawn , Banerjee Payal , Sullivan Catherine , Gupta Abha R. , Kriegstein Arnold R. , Corbin Joshua G.
Published: May 2020

Background

Studies of individuals with autism spectrum disorder (ASD) have revealed a strong multigenic basis with the identification of hundreds of ASD susceptibility genes. ASD is characterized by social deficits and a range of other phenotypes, implicating complex genetics and involvement of a variety of brain regions. However, how mutations and mis-expression of select gene sets are associated with the behavioral components of ASD remains unknown. We reasoned that for genes to be associated with ASD core behaviors they must be: (1) expressed in brain regions relevant to ASD social behaviors and (2) expressed during the ASD susceptible window of brain development.

Methods

Focusing on the amygdala, a brain region whose dysfunction has been highly implicated in the social component of ASD, we mined publicly available gene expression databases to identify ASD-susceptibility genes expressed during human and mouse amygdala development. We found that a large cohort of known ASD susceptibility genes is expressed in the developing human and mouse amygdala. We further performed analysis of single-nucleus RNA-seq (snRNA-seq) data from microdissected amygdala tissue from five ASD and five control human postmortem brains ranging in age from 4 to 20 years to elucidate cell type specificity of amygdala-expressed genes and their dysregulation in ASD.

Results

Our analyses revealed that of the high-ranking ASD susceptibility genes, 80 are expressed in both human and mouse amygdala during fetal to early postnatal stages of development. Our human snRNA-seq analyses revealed cohorts of genes with altered expression in the ASD amygdala postnatally, especially within excitatory neurons, with dysregulated expression of seven genes predicted from our datamining pipeline.

Limitations

We were limited by the ages for which we were able to obtain human tissue; therefore, the results from our datamining pipeline approach will require validation, to the extent possible, in human tissue from earlier developmental stages.

Conclusions

Our pipeline narrows down the number of amygdala-expressed genes possibly involved in the social pathophysiology of ASD. Our human single-nucleus gene expression analyses revealed that ASD is characterized by changes in gene expression in specific cell types in the early postnatal amygdala.
Intravenous infusion of human umbilical cord Wharton’s jelly-derived mesenchymal stem cells as a potential treatment for patients with COVID-19 pneumonia
Authors: Zhang Yingxin , Ding Jie , Ren Shaoda , Wang Weihua , Yang Yapei , Li Shuangjing , Meng Min , Wu Tiejun , Liu Daliang , Tian Suochen , Tian Hui , Chen Shuangfeng , Zhou Changhui
Published: May 2020

The novel coronavirus disease 2019 (COVID-19) has grown to be a global public health emergency since patients were first detected in Wuhan, China. Thus far, no specific drugs or vaccines are available to cure the patients with COVID-19 infection. The immune system and inflammation are proposed to play a central role in COVID-19 pathogenesis. Mesenchymal stem cells (MSCs) have been shown to possess a comprehensive powerful immunomodulatory function. Intravenous infusion of MSCs has shown promising results in COVID-19 treatment. Here, we report a case of a severe COVID-19 patient treated with human umbilical cord Wharton’s jelly-derived MSCs (hWJCs) from a healthy donor in Liaocheng People’s Hospital, China, from February 24, 2020. The pulmonary function and symptoms of the patient with COVID-19 pneumonia was significantly improved in 2 days after hWJC transplantation, and recovered and discharged in 7 days after treatment. After treatment, the percentage and counts of lymphocyte subsets (CD3+, CD4+, and CD8+ T cell) were increased, and the level of IL-6, TNF-α, and C-reactive protein is significantly decreased after hWJC treatment. Thus, the intravenous transplantation of hWJCs was safe and effective for the treatment of patients with COVID-19 pneumonia, especially for the patients in a critically severe condition. This report highlights the potential of hWJC infusions as an effective treatment for COVID-19 pneumonia.
Role of CD133 in human embryonic stem cell proliferation and teratoma formation
Authors: Wang Hua , Gong Peng , Li Jie , Fu Yudong , Zhou Zhongcheng , Liu Lin
Published: May 2020

Background

Pluripotent stem cells (PSCs), including human embryonic stem cells (hESCs), hold great potential for regenerative medicine and cell therapy. One of the major hurdles hindering the clinical development of PSC-based therapy is the potential risk of tumorigenesis. CD133 (Prominin 1, PROM1) is a transmembrane protein whose mRNA and glycosylated forms are highly expressed in many human cancer cell types. CD133 also serves as a cancer stem cell (CSC) marker associated with cancer progression and patient outcome. Interestingly, CD133 is highly expressed in hESCs as well as in human preimplantation embryos, but its function in hESCs has remained largely unknown.

Methods

CD133 knockout hESC WA26 cell line was generated with CRISPR/Cas9. CD133 knockout and wide type hESC lines were subjected to pluripotency, proliferation, telomere biology, and teratoma tests; the related global changes and underlying mechanisms were further systemically analyzed by RNA-seq.

Results

CD133 deficiency did not affect hESC pluripotency or in vivo differentiation into three germ layers but significantly decreased cell proliferation. RNA-seq revealed that CD133 deficiency dysregulated the p53, PI3K-Akt, AMPK, and Wnt signaling pathways. Alterations in these pathways have been implicated in tumor proliferation and apoptotic escape.

Conclusions

Our data imply that CD133 could be an additional target and used as a selective marker to sort and eliminate undifferentiated cells in reducing potential teratoma formation risk of hESCs in regenerative medicine.
EDock: blind protein–ligand docking by replica-exchange monte carlo simulation
Authors: Zhang Wenyi , Bell Eric W. , Yin Minghao , Zhang Yang
Published: May 2020

Protein–ligand docking is an important approach for virtual screening and protein function annotation. Although many docking methods have been developed, most require a high-resolution crystal structure of the receptor and a user-specified binding site to start. This information is, however, not available for the majority of unknown proteins, including many pharmaceutically important targets. Developing blind docking methods without predefined binding sites and working with low-resolution receptor models from protein structure prediction is thus essential. In this manuscript, we propose a novel Monte Carlo based method, EDock, for blind protein–ligand docking. For a given protein, binding sites are first predicted by sequence-profile and substructure-based comparison searches with initial ligand poses generated by graph matching. Next, replica-exchange Monte Carlo (REMC) simulations are performed for ligand conformation refinement under the guidance of a physical force field coupled with binding-site distance constraints. The method was tested on two large-scale datasets containing 535 protein–ligand pairs. Without specifying binding pockets on the experimental receptor structures, EDock achieves on average a ligand RMSD of 2.03 Å, which compares favorably with state-of-the-art docking methods including DOCK6 (2.68 Å) and AutoDock Vina (3.92 Å). When starting with predicted models from I-TASSER, EDock still generates reasonable docking models, with a success rate 159% and 67% higher than DOCK6 and AutoDock Vina, respectively. Detailed data analyses show that the major advantage of EDock lies in reliable ligand binding site predictions and extensive REMC sampling, which allows for the implementation of multiple van der Waals weightings to accommodate different levels of steric clashes and cavity distortions and therefore enhances the robustness of low-resolution docking with predicted protein structures.
Effect of the selection pressure of vaccine antibodies on evolution of H9N2 avian influenza virus in chickens
Authors: Su Hailong , Zhao Yu , Zheng Lirong , Wang Shifeng , Shi Huoying , Liu Xiufan
Published: May 2020

H9N2 avian influenza virus has spread worldwide, and vaccination with an inactivated virus is currently the major prevention method in China. To further understand the effect of the selection pressure from antibodies on the evolution of H9N2 avian influenza virus, F/98 (A/Chicken/Shanghai/F/98), which is the vaccine representative of H9N2 avian influenza virus in East China, was used for serial passaging for 20 generations in chickens with and without vaccination. After plaque purification from trachea and lung tissues, 390 quasispecies were obtained. The second-generation quasispecies under the selection pressure of vaccine antibodies had undergone 100% antigen variation, while after passaging to the fifth generation, only 30–40% of the quasispecies displayed antigen variation when there was no selection pressure of vaccine antibodies, implying that the selection pressure of vaccine antibodies promotes the antigen variation of F/98. We found for the first time that there were three mutation hotspots in the HA genes of the quasispecies under the selection pressure of vaccine antibodies, which were K131R, A168T, and N201D. Moreover, under the selection pressure of vaccine antibodies, 10 amino acids (67–76) of the NA protein of all quasispecies were deleted, and PB2 of the quasispecies had undergone a high-frequency R355K mutation. However, without selection pressure of vaccine antibodies, NP had undergone two high-frequency mutations, namely, V186I and L466I, and a high-frequency mutation of L77I appeared in the NS gene. This result shows that the vaccine antibody selection pressure could control and regulate gene variation of the F/98 virus. Compared to that of the parental virus F/98, the EID50 of the twentieth passaged virus under the selection pressure of vaccine antibodies did not change, while the EID50 of the twentieth passaged virus without selection pressure of vaccine antibodies was significantly enhanced by 794 times. Furthermore, the twentieth passaged virus with selection pressure from vaccine antibodies lost its lethal ability in embryonated chicken eggs, whereas the EID50 of the twentieth passaged virus without selection pressure of vaccine antibodies increased to 6.3 times that of the F/98 strain. All the above results show that the selection pressure of vaccine antibodies promotes the antigen variation of H9N2 avian influenza virus and plays a role in regulating and controlling gene mutation of H9N2 avian influenza virus.
A coupled system of generalized Sturm–Liouville problems and Langevin fractional differential equations in the framework of nonlocal and nonsingular derivatives
Authors: Baleanu D. , Alzabut J. , Jonnalagadda J. M. , Adjabi Y. , Matar M. M.
Published: May 2020

In this paper, we study a coupled system of generalized Sturm–Liouville problems and Langevin fractional differential equations described by Atangana–Baleanu–Caputo (ABC for short) derivatives whose formulations are based on the notable Mittag-Leffler kernel. Prior to the main results, the equivalence of the coupled system to a nonlinear system of integral equations is proved. Once that has been done, we show in detail the existence–uniqueness and Ulam stability by the aid of fixed point theorems. Further, the continuous dependence of the solutions is extensively discussed. Some examples are given to illustrate the obtained results.
Parameter interval of positive solutions for a system of fractional difference equation
Authors: Ghanbari Kazem , Haghi Tahereh
Published: May 2020

This paper deals with a typical system of Caputo fractional difference equations. Using the Guo–Krasnosel’skii fixed point theorem, we find a parameter interval for which at least one positive solution of the system exists. We give two examples to illustrate the results.
Impact of reduction in contact time activity of infected individuals on the dynamics and control of directly transmitted respiratory infections in SIR models
Authors: Safan Muntaser
Published: May 2020

This paper aims to study the impact of using an educational strategy on reducing the efforts needed to control respiratory transmitted infections represented by SIR models, taking into account heterogeneity in contacts between infected and non-infected individuals. Therefore, a new incidence function, in which the difference in contact time activity between infected and non-infected individuals is taken into account, is formulated. Equilibrium and stability analyses of the model have been carried out. The model has been extended to include the effect of herd immunity and the analysis showed that the higher the percent reduction$\widehat{P}_{r}$Pˆrin the contact-activity time of infected individuals is, the lower the critical vaccination coverage level$p_{c}$pcrequired to eliminate the infection is, and therefore, the lower the infection’s minimum elimination effort is. Another extension of the basic model to include a control strategy based on treating infected individuals at rateαwith a maximum capacity treatment$\mathcal{I}$Ihas been considered. The equilibrium analysis showed the existence of multiple subcritical and supercritical endemic equilibria, while the stability analysis showed that the model exhibits a Hopf bifurcation. Simulations showed that the higher the maximum treatment capacity$\mathcal{I}$Iis, the lower the value of the critical reduction in infected individuals’ time activity$P_{r}^{\star}$Pr⋆, at which a Hopf bifurcation is generated, is. Simulations with parameter values corresponding to the case of influenza A have been carried out.
Early discontinuation of empirical antibiotic treatment in neutropenic patients with acute myeloid leukaemia and high-risk myelodysplastic syndrome
Authors: Niessen F. A. , van Mourik M. S. M. , Bruns A. H. W. , Raijmakers R. A. P. , de Groot M. C. H. , van der Bruggen T.
Published: May 2020

Introduction

Current guidelines advocate empirical antibiotic treatment (EAT) in haematological patients with febrile neutropenia. However, the optimal duration of EAT is unknown. In 2011, we have introduced a protocol, promoting discontinuation of carbapenems as EAT after 3 days in most patients and discouraging the standard use of vancomycin. This study assesses the effect of introducing this protocol on carbapenem and vancomycin use in high-risk haematological patients and its safety.

Methods

A retrospective before-after study was performed comparing a cohort from 2007 to 2011 (period I, before restrictive EAT use) with a cohort from 2011 to 2014 (period II, restrictive EAT use). Neutropenic episodes related to chemotherapy or stem cell transplantation (SCT) in patients with acute myeloid leukaemia (AML) or high-risk myelodysplastic syndrome (MDS) were analysed. The primary outcome was the use of carbapenems and vancomycin as EAT during neutropenia, expressed as days of therapy (DOT)/100 neutropenic days and analysed with interrupted time series (ITS). Also the use of other antibiotics was analysed. Safety measurements included 30-day mortality, ICU admittance within 30 days after start of EAT and positive blood cultures with carbapenem-susceptible microorganisms.

Results

Three hundred sixty-two neutropenic episodes with a median duration of 18 days were analysed, involving 201 patients. ITS analysis showed decreased carbapenem use with a step change of − 16.1 DOT/100 neutropenic days (95% CI − 26.77 to − 1.39) and an overall reduction of 21.6% (8.7 DOT/100 neutropenic days). Vancomycin use decreased with a step change of − 13.7 DOT/100 neutropenic days (95% CI − 23.75 to − 3.0) and an overall reduction of 54.7% (14.6 DOT/100 neutropenic days). The use of all antibiotics combined decreased from 155.6 to 138 DOT/100 neutropenic days, a reduction of 11.3%. No deaths directly related to early discontinuation of EAT were identified, also no notable difference in ICU-admission (9/116 in period I, 9/152 in period II) and positive blood cultures (4/116 in period I, 2/152 in period II) was detected.

Conclusion

The introduction of a protocol promoting restrictive use of EAT resulted in reduction of carbapenem and vancomycin use and appears to be safe in AML or high-risk MDS patients with febrile neutropenia during chemotherapy or SCT.
Multidrug-resistant tuberculosis transmission among middle school students in Zhejiang Province, China
Authors: Zhang Yu , Zhou Lin , Liu Zheng-Wei , Chai Cheng-Liang , Wang Xiao-Meng , Jiang Jian-Min , Chen Song-Hua
Published: May 2020

Background

Despite significant advancements in the treatment and diagnosis of tuberculosis (TB) over the past decade, drug-resistant TB remains an increasing threat to public health. TB outbreaks are most commonly reported in schools considering the delay in TB diagnosis, sustained contact, and overcrowding observed in schools. This report describes multidrug-resistant TB (MDR-TB) transmission in a school in Zhejiang Province. We aimed to raise awareness regarding MDR-TB transmission among students.

Case presentation

The index patient was a 16-year-old girl in the second year of junior middle school in Zhejiang Province, China, who had been experiencing persistent cough and expectoration for 37 days since 1 March 2014. She tested positive for smear pulmonary and extrapulmonary TB on 8 April 2014 and was subsequently diagnosed with MDR-TB on 1 May 2014. However, the patient was resistant to isoniazid, rifampicin, ethambutol, and streptomycin. Thus, she was suspended from school for anti-TB treatment. All 54 students who were in close contact with the index patient in the same class were screened, and 5 tested positive on the tuberculin skin test. Their exposure time to the index patient was approximately 37 days. Three classmates were subsequently diagnosed with MDR-TB, with similar resistance profiles nearly two years later. Their average discovery delay was 55 days. These three classmates were also suspended from school for anti-TB treatment. During the treatment period, four students visited the local TB-designated hospital for further consultation every month and were followed up once a month by the local community health service center until they were completely cured.

Conclusions

Discovery delay for an index patient played a primary role in MDR-TB transmission inside the school. To immediately detect TB, morning examinations in schools should be performed. TB trackers and case managers should work closely with public health workers and physicians in cases of TB outbreaks or transmissions involving students. Moreover, individuals who are in close contact with MDR-TB patients should undergo careful clinical follow-up for at least two years. Implementing a joint examination strategy to ensure early detection, diagnosis, and treatment of MDR-TB transmission is recommended.
Blue whale (Balaenoptera musculus) sightings off the coast of Virginia
Authors: Engelhaupt Dan T. , Pusser Todd , Aschettino Jessica M. , Engelhaupt Amy G. , Cotter Mark P. , Richlen Michael F. , Bell Joel T.
Published: May 2020

We report on two sightings of individual blue whales (Balaenoptera musculus) off the coast of Virginia during marine mammal surveys. On 11 April 2018, during a vessel survey off the coast of Virginia, a single blue whale was observed approximately 100 km east-northeast of Virginia Beach. On 10 February 2019, another single blue whale was recorded during an aerial survey approximately 135 km east-southeast of Virginia Beach. These observations mark the first time this endangered species has been documented with photographs off the coast of Virginia, and represent the southernmost confirmed sightings in waters of the United States Atlantic Exclusive Economic Zone (EEZ). At the time of the vessel observation, numerous fin whales (Balaenoptera physalus), humpback whales (Megaptera novaeangliae), and North Atlantic right whales (Eubalaena glacialis), were observed within the same approximately 8 km2area as the blue whale. For the aerial sighting, the blue whale was seen feeding among at least 15 fin whales in an area approximately 4 km2. These sightings contribute to the small body of information existing for the late winter/early spring distribution of blue whales in waters of the western North Atlantic.
Pattern of recovery and outcomes of patient reported physical function and pain interference after ankle fusion: a retrospective cohort study
Authors: Kohring Jessica M. , Houck Jeffrey R. , Oh Irvin , Flemister Adolf S. , Ketz John P. , Baumhauer Judith F.
Published: May 2020

Background

Research on outcomes after ankle fusion focuses on basic activities of daily living, fusion rates, and gait parameters. Little has been reported on the patient’s perspective after surgery. The purpose of this study was to determine the change in patient reported physical function and pain interference after ankle fusion surgery to guide patient expectations and improve provider communication.

Methods

This was a retrospective review of prospectively collected patient reported outcome measurement information system (PROMIS) data in 88 ankle arthrodesis procedures performed from May 2015 to March 2018. The PROMIS Physical function (PF) and pain interference (PI) measures were collected as routine care. Linear mixed models were used to assess differences at each follow-up point for PF and PI. Preoperative to last follow-up in the 120–365 day interval was assessed using analysis of variance. Outcomes included T-scores, z-scores, and PROMIS-Preference (PROPr) utility scores for PF and PI and the percentage of patients improving by at least 4 T-score points.

Results

The linear mixed model analysis for PF after the 120–149 days, and for PI, after 90–119 days, indicated recovery plateaued at 39–40 for PF and 57–59 for PI T-scores. The change in the PI T-score was the greatest with a mean T-score improvement of − 5.4 (95% CI − 7.7 to − 3.1). The proportion of patients improving more than 4 points was 66.2% for either PF or PI or both. The change in utility T-scores for both PF (0.06, 95% CI 0.02 to 0.11) and PI (0.15, 95% CI 0.09 to 0.20) was significantly improved, however, only PI approached clinical significance.

Conclusion

Average patients undergoing ankle fusion experience clinically meaningful improvement in pain more so than physical function. Average patient recovery showed progressive improvement in pain and function until the four-month postoperative time point. Traditional dogma states that recovery after an ankle fusion maximizes at a year, however based on the findings in this study, 4 months is a more accurate marker of recovery. A decline in function or an increase in pain after 4 months from surgery may help to predict nonunion and other complications after ankle arthrodesis.

Level of evidence

Level II, prospective single cohort study.
Effect of fluoride on the learning and memory ability of larvae of Zaprionus indianus
Authors: Mishra Diksha , Kumari Rishu , Ranjan Smita , Yasmin Shahla
Published: May 2020

Background

Many pesticides contain fluoride that enters the food chain and affect the non-target organisms. Fluoride is a known neurotoxin and may cause neurobehavioral defects. A study was conducted to see the effect of fluoride on the learning and memory ability of larvae of Zaprionus indianus. The learning and memory ability of 2nd instar larvae of normal (control) and sodium fluoride (NaF)-treated Zaprionus indianus was compared.

Results

Sublethal concentration of NaF for Z. indianus was found to be 0.8 ppm. Olfactory assay results showed that the larvae of normal (control) Z. indianus had better learning and memory ability in comparison to NaF-treated larvae.

Conclusions

This study indicates that the insects exposed to pesticides containing fluoride may have difficulty in locating food sources and carrying out pollination.
A rare chest X-ray sign in the diagnosis of an intracardiac bullet: case report
Authors: Osman Mohamed , Khalil Reham , Abdalla Ahmed Hany , Katta Azza , Nashef Samer , Elameen Sameh
Published: May 2020

Background

Gunshot injuries to the heart are often seen in cardiac surgical practice. Victims are usually investigated with various types of imaging modalities, including simple chest X-ray (CXR) which is a primary imaging modality that can easily locate a bullet and is useful in monitoring before surgical intervention as bullets may migrate.

Case presentation

A 32-year-old man was admitted as an emergency in a primary hospital after being injured by a gunshot to the chest. The bullet entry was over the back of the left shoulder with no exit point seen. The chest X-ray showed left pleural effusion and a retained intrathoracic bullet. A chest drain was inserted and drained 2200 ml of blood. Computed tomography (CT) scan showed an intracardiac bullet associated with left lower lobe contusion and left-sided hemothorax. He was urgently transferred to theater for exploration via left thoracotomy. The bullet could not be found so the inlet point in the left ventricle was sutured. After stabilizing the patient, he was referred to a specialized cardiac center for further management.

The patient arrived at our center 2 days after the injury, fully conscious and hemodynamically stable. On arrival, chest X-rays were obtained to rule out possible migration of the bullet and revealed that the retained bullet was still within the cardiac silhouette. The X-ray appearance of the bullet showed a characteristically double contour, strongly suggesting that the bullet had lodged in the heart muscle and was moving with each heartbeat.

The patient was transferred to the theater for median sternotomy. The aorta, superior vena cava, and inferior vena cava were cannulated, and cardiopulmonary bypass was initiated. The aorta was cross-clamped and the cardioplegia was given. Palpation of the still heart readily identified the bullet within the interventricular septum. The left ventricle was opened 1 cm from the left anterior descending artery just on top of the bullet. The bullet was successfully retrieved. The bullet was transfixing the septum causing a small ventricular septal defect which was closed using a Teflon patch and the ventricle was repaired.

Conclusion

The double contour appearance of the bullet indicates that the bullet is moving and strongly suggests an intramyocardial position.
Response of economic growth to the dynamics of service sector in Nigeria
Authors: Adetokunbo Abiodun Moses , Edioye Ochuwa Priscillia
Published: May 2020

The misconception of services as being non-productive has led to the neglect of the service sector in both economic theory and applied economic researches. The Nigerian economy highly depends on the oil sector to generate revenue for the entire economy. This study examines the response of economic growth to the dynamics of the service sector in Nigeria from the windows of governance indicators. Using annual data series, endogenous growth model, and autoregressive distributed lag technique, transportation and communication service subsector is significant and positively related to economic growth. Health service subsector and transportation and communication subservice sector are significant and positively related to economic growth when governance indicators were accounted for. Interaction of the subservice sectors with governance indicators shows that none of the service subsectors were significant but were positively related to economic growth. The study shows that the activities of the education subsector have not contributed significantly to economic growth. Thus, for education to contribute positively to economic growth there is a need for increase in budgetary allocation to education subsector. Efforts made to control corruption and promote government effectiveness should be reviewed frequently to checkmate the processes of governance, so that bureaucratic processes would not hinder services from contributing significantly to economic growth.
Nonthyroidal Illness Syndrome and Hypothyroidism in Ischemic Heart Disease Population: A Systematic Review and Meta-Analysis
Authors: Chang Chun-Yu , Chien Yung-Jiun , Lin Po-Chen , Chen Chien-Sheng , Wu Meng-Yu
Published: May 2020

Context

The association of non-thyroidal illness syndrome (NTIS) and hypothyroidism with the prognosis in ischemic heart disease (IHD) population is inconclusive.

Objective

We aimed to evaluate the influence of NTIS and hypothyroidism on all-cause mortality and major adverse cardiac events (MACE) in IHD population.

Data Sources

We searched PubMed, EMBASE, Scopus, Web of Science, and Cochrane Library from inception through February 17, 2020.

Study Selection

Original articles enrolling IHD patients, comparing all-cause mortality and MACE of NTIS and hypothyroidism with those of euthyroidism, and providing sufficient information for meta-analysis were considered eligible.

Data Extraction

Relevant information and numerical data were extracted for methodological assessment and meta-analysis.

Data Synthesis

Twenty-three studies were included. The IHD population with NTIS was associated with higher risk of all-cause mortality (hazard ratio [HR] = 2.61; 95% confidence interval [CI] = 1.89-3.59) and MACE (HR = 2.22; 95% CI = 1.71-2.89) than that without. In addition, the IHD population with hypothyroidism was also associated with higher risk of all-cause mortality (HR = 1.47; 95% CI = 1.10-1.97) and MACE (HR = 1.53; 95% CI = 1.19-1.97) than that without. In the subgroup analysis, the acute coronary syndrome (ACS) subpopulation with NTIS was associated with higher risk of all-cause mortality (HR = 3.30; 95% CI = 2.43-4.48) and MACE (HR = 2.19; 95% CI = 1.45-3.30). The ACS subpopulation with hypothyroidism was also associated with higher risk of all-cause mortality (HR = 1.67; 95% CI = 1.17-2.39).

Conclusions

The IHD population with concomitant NTIS or hypothyroidism was associated with higher risk of all-cause mortality and MACE. Future research is required to provide evidence of the causal relationship and to elucidate whether normalizing thyroid function parameters can improve prognosis.
The zebrafish as a novel model for the in vivo study of Toxoplasma gondii replication and interaction with macrophages
Authors: Yoshida Nagisa , Domart Marie-Charlotte , Peddie Christopher J. , Yakimovich Artur , Mazon-Moya Maria J. , Hawkins Thomas A. , Collinson Lucy , Mercer Jason , Frickel Eva-Maria , Mostowy Serge
Published: May 2020

Toxoplasma gondii is an obligate intracellular parasite capable of invading any nucleated cell. Three main clonal lineages (type I, II, III) exist and murine models have driven the understanding of general and strain-specific immune mechanisms underlying Toxoplasma infection. However, murine models are limited for studying parasite-leukocyte interactions in vivo, and discrepancies exist between cellular immune responses observed in mouse versus human cells. Here, we developed a zebrafish infection model to study the innate immune response to Toxoplasma in vivo. By infecting the zebrafish hindbrain ventricle, and using high-resolution microscopy techniques coupled with computer vision-driven automated image analysis, we reveal that Toxoplasma invades brain cells and replicates inside a parasitophorous vacuole to which type I and III parasites recruit host cell mitochondria. We also show that type II and III strains maintain a higher infectious burden than type I strains. To understand how parasites are cleared in vivo, we further analyzed Toxoplasma-macrophage interactions using time-lapse microscopy and three-dimensional correlative light and electron microscopy (3D CLEM). Time-lapse microscopy revealed that macrophages are recruited to the infection site and play a key role in Toxoplasma control. High-resolution 3D CLEM revealed parasitophorous vacuole breakage in brain cells and macrophages in vivo, suggesting that cell-intrinsic mechanisms may be used to destroy the intracellular niche of tachyzoites. Together, our results demonstrate in vivo control of Toxoplasma by macrophages, and highlight the possibility that zebrafish may be further exploited as a novel model system for discoveries within the field of parasite immunity.

This article has an associated First Person interview with the first author of the paper.
Ontogenetic variation in the hearing sensitivity of black sea bass (Centropristis striata) and the implications of anthropogenic sound on behavior and communication
Authors: Stanley Jenni A. , Caiger Paul E. , Phelan Beth , Shelledy Katharine , Mooney T. Aran , Van Parijs Sofie M.
Published: May 2020

Black sea bass (Centropristis striata) is an important fish species in both commercial and recreational fisheries of southern New England and the mid-Atlantic Bight. Due to the intense urbanization of these waters, this species is subject to a wide range of anthropogenic noise pollution. Concerns that C. striata are negatively affected by pile driving and construction noise predominate in areas earmarked for energy development. However, as yet, the hearing range of C. striata is unknown, making it hard to evaluate potential risks. This study is a first step in understanding the effects of anthropogenic noise on C. striata by determining the auditory bandwidth and thresholds of this species using auditory evoked potentials (AEPs), creating pressure and acceleration audiograms. These physiological tests were conducted on wild-caught C. striata in three size/age categories. Results showed that juvenile C. striata significantly had the lowest thresholds, with hearing sensitivity decreasing in the larger size classes. Furthermore, Centropristis striata has fairly sensitive hearing relative to other related species. Preliminary investigations into the mechanisms of their hearing ability were undertaken with gross dissections and an opportunistic micro computed tomography image to address the auditory structures including otoliths and swimbladder morphology. Crucially, the hearing range of C. striata, and their most sensitive frequencies, directly overlap with high-amplitude anthropogenic noise pollution such as shipping and underwater construction.
Polarized light sensitivity in Pieris rapae is dependent on both color and intensity
Authors: Blake Adam J. , Hahn Gina S. , Grey Hayley , Kwok Shelby A. , McIntosh Deby , Gries Gerhard
Published: May 2020

There is an ever increasing number of arthropod taxa shown to have polarization sensitivity throughout their compound eyes. However, the downstream processing of polarized reflections from objects is not well understood. The small white butterfly, Pieris rapae, has been demonstrated to exploit foliar polarized reflections, specifically the degree of linear polarization (DoLP), to recognize host plants. The well-described visual system of P. rapae includes several photoreceptor types (red, green, blue) that are sensitive to polarized light. Yet, the roles and interaction among photoreceptors underlying the behavioral responses of P. rapae to stimuli with different DoLPs remain unknown. To investigate potential neurological mechanisms, we designed several two-choice behavioral bioassays, displaying plant images on paired LCD monitors which allowed for independent control of polarization, color and intensity. When we presented choices between stimuli that differed in either color or DoLP, both decreasing and increasing the intensity of the more attractive stimulus reduced the strength of preference. This result suggests differences in color and DoLP are perceived in a similar manner. When we offered a DoLP choice between plant images manipulated to minimize the response of blue, red, or blue and red photoreceptors, P. rapae shifted its preference for DoLP, suggesting a role for all of these photoreceptors. Modeling of P. rapae photoreceptor responses to test stimuli suggests that differential DoLP is not perceived solely as a color difference. Our combined results suggest that P. rapae females process and interpret polarization reflections in a way different from that described for other polarization-sensitive taxa.
The impact of community containment implementation timing on the spread of COVID-19: A simulation study
Authors: Mohsen Attayeb , Alarabi Ahmed
Published: May 2020

Background: Community containment is one of the common methods used to mitigate infectious disease outbreaks. The effectiveness of such a method depends on how strictly it is applied and the timing of its implementation. An early start and being strict is very effective; however, at the same time, it impacts freedom and economic opportunity. Here we created a simulation model to understand the effect of the starting day of community containment on the ﬁnal outcome, that is, the number of those infected, hospitalized and those that died, as we followed the dynamics of COVID-19 pandemic.

Methods: We used a stochastic recursive simulation method to apply disease outbreak dynamics measures of COVID-19 as an example to simulate disease spread. Parameters are allowed to be randomly assigned between higher and lower values obtained from published COVID-19 literature.

Results: We simulated the dynamics of COVID-19 spread, calculated the number of active infections, hospitalizations and deaths as the outcome of our simulation and compared these results with real world data. We also represented the details of the spread in a network graph structure, and shared the code for the simulation model to be used for examining other variables.

Conclusions: Early implementation of community containment has a big impact on the ﬁnal outcome of an outbreak.