bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biotransformation Capacity of Zebrafish (Danio rerio) Early Life Stages: Functionality of the Mercapturic Acid Pathway
Authors: Tierbach Alena , Groh Ksenia J , Schönenberger René , Schirmer Kristin , Suter Marc J -F 
Published: May 2020

AbstractZebrafish (Danio rerio) early life stages offer a versatile model system to study the efficacy and safety of drugs or other chemicals with regard to human and environmental health. This is because, aside from the well-characterized genome of zebrafish and the availability of a broad range of experimental and computational research tools, they are exceptionally well suited for high-throughput approaches. Yet, one important pharmacokinetic aspect is thus far only poorly understood in zebrafish embryo and early larvae: their biotransformation capacity. Especially, biotransformation of electrophilic compounds is a critical pathway because they easily react with nucleophile molecules, such as DNA or proteins, potentially inducing adverse health effects. To combat such adverse effects, conjugation reactions with glutathione and further processing within the mercapturic acid pathway have evolved. We here explore the functionality of this pathway in zebrafish early life stages using a reference substrate (1-chloro-2,4-dinitrobenzene, CDNB). With this work, we show that zebrafish embryos can biotransform CDNB to the respective glutathione conjugate as early as 4 h postfertilization. At all examined life stages, the glutathione conjugate is further biotransformed to the last metabolite of the mercapturic acid pathway, the mercapturate, which is slowly excreted. Being able to biotransform electrophiles within the mercapturic acid pathway shows that zebrafish early life stages possess the potential to process xenobiotic compounds through glutathione conjugation and the formation of mercapturates. The presence of this chemical biotransformation and clearance route in zebrafish early life stages supports the application of this model in toxicology and chemical hazard assessment.
Lead Impairs the Development of Innate Lymphoid Cells by Impeding the Differentiation of Their Progenitors
Authors: Zhu Tingting , Zhao Yifan , Zhang Peng , Shao Yiming , He Jinyi , Xue Peng , Zheng Weiwei , Qu Weidong , Jia Xiaodong , Zhou Zhijun , Lu Rongzhu , He Miao , Zhang Yubin 
Published: May 2020

Abstract
Lead (Pb) is a heavy metal toxic to the immune system, yet the influence of Pb on innate lymphoid cells (ILC) remains to be defined. In this study, we found that occupationally relevant level of Pb exposure impaired ILC development at the progenitor level by activating Janus Kinase1. C57BL/6 mice treated with 1250 ppm, but not 125 ppm Pb acetic via drinking water for 8 weeks had reduced number of mature ILC, which was not caused by increased apoptosis or suppressed proliferation. Conversely, Pb increased the number of innate lymphoid cell progenitors (ILCP) in the bone marrow. The discordant observation indicated that an obstruction of ILCP differentiation into mature ILC during Pb exposure existed. Pb directly acted on ILCP to suppress their proliferation, indicating that ILCP were less activated during Pb exposure. Reciprocal ILCP transplantation assay confirmed that Pb impeded the differentiation of ILCP into mature ILC, as ILCP gave rise to fewer mature ILC in Pb-treated recipients compared with control recipients. In vitro assays suggested that the obstruction of ILCP differentiation by Pb exposure was due to increased activation of Janus Kinase1. Thus, Pb impeded ILCP differentiation into mature ILC to result in an accumulation of ILCP in the bone marrow and the resultant decreased number of mature ILC in lymphoid and nonlymphoid tissues in mice. Moreover, by analyses of ILC and ILCP in peripheral blood mononuclear cells of human subjects occupationally exposed to Pb, we revealed that Pb might also impede the development of ILC in human.
Dexmedetomidine Activation of Dopamine Neurons in the Ventral Tegmental Area Attenuates the Depth of Sedation in Mice
Authors: Qiu Gaolin , Wu Ying , Yang Zeyong , Li Long , Zhu Xiaona , Wang Yiqiao , Sun Wenzhi , Dong Hailong , Li Yuanhai , Hu Ji 
Published: May 2020

Background
Dexmedetomidine induces a sedative response that is associated with rapid arousal. To elucidate the underlying mechanisms, the authors hypothesized that dexmedetomidine increases the activity of dopaminergic neurons in the ventral tegmental area, and that this action contributes to the unique sedative properties of dexmedetomidine.

Methods
Only male mice were used. The activity of ventral tegmental area dopamine neurons was measured by a genetically encoded Ca2+ indicator and patch-clamp recording. Dopamine neurotransmitter dynamics in the medial prefrontal cortex and nucleus accumbens were measured by a genetically encoded dopamine sensor. Ventral tegmental area dopamine neurons were inhibited or activated by a chemogenetic approach, and the depth of sedation was estimated by electroencephalography.

Results
Ca2+ signals in dopamine neurons in the ventral tegmental area increased after intraperitoneal injection of dexmedetomidine (40 μg/kg; dexmedetomidine, 16.917 [14.882; 21.748], median [25%; 75%], vs. saline, –0.745 [–1.547; 0.359], normalized data, P = 0.001; n = 6 mice). Dopamine transmission increased in the medial prefrontal cortex after intraperitoneal injection of dexmedetomidine (40 μg/kg; dexmedetomidine, 10.812 [9.713; 15.104], median [25%; 75%], vs. saline, –0.498 [–0.664; –0.355], normalized data, P = 0.001; n = 6 mice) and in the nucleus accumbens (dexmedetomidine, 8.543 [7.135; 11.828], median [25%; 75%], vs. saline, –0.329 [–1.220; –0.047], normalized data, P = 0.001; n = 6 mice). Chemogenetic inhibition or activation of ventral tegmental area dopamine neurons increased or decreased slow waves, respectively, after intraperitoneal injection of dexmedetomidine (40 μg/kg; delta wave: two-way repeated measures ANOVA, F[2, 33] = 8.016, P = 0.002; n = 12 mice; theta wave: two-way repeated measures ANOVA, F[2, 33] = 22.800, P < 0.0001; n = 12 mice).

Conclusions
Dexmedetomidine activates dopamine neurons in the ventral tegmental area and increases dopamine concentrations in the related forebrain projection areas. This mechanism may explain rapid arousability upon dexmedetomidine sedation.

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Attending Physician's Attitudes Toward Podcasting as a Source of Medical Education: An Exploratory Study
Authors: Tarchichi Tony R. , Szymusiak John 
Published: May 2020

Introduction:
People are increasingly consuming information on-demand. Podcasting is a growing medium for education in an on-demand world. There is a paucity of data on podcasting as a means of continuing medical education (CME) for attending physicians.

Methods:
The authors performed an exploratory survey of a convenience sample of listeners to a Pediatric Hospital Medicine podcast to learn about their attitudes regarding podcasting. A 17-question survey consisting of demographic data, attitudinal questions, and qualitative questions was administered electronically in February 2018.

Results:
At the time of the survey, the 12 podcast episodes were downloaded 17,288 times, with 162 CME credits being issued. Of 129 respondents, 75.2% were attendings. The majority agreed the podcast was of “high educational value” and was of equal or better educational value as medical journals or national conferences. Qualitative content analysis revealed listeners valued the convenience of the podcast, and community-based hospitalists felt the podcast connected them to the broader hospitalist community.

Discussion:
Our respondents found podcasting to be a beneficial and convenient learning method. The ability to apply for CME credit was not a major motivation for listening. Further research is needed to investigate more objective outcomes and assess attitudes of a random sampling of physicians as opposed to a self-selected sample.
One Hospital's Call to Action: Preparing Faculty for a New Medical School
Authors: Nonaillada Jeannine 
Published: May 2020

Introduction:
This is a single-site feasibility project where a new, 3-year medical school was created. To respond to emergent teaching preparedness and leadership readiness in new administrative roles, an educational series taught by clinical faculty and staff was offered at noontime.

Methods:
The series focused on administrative skills, teaching techniques, and student success. The curricular strategies employed were the menu approach for educational offerings and spiral sequencing of curricula. Faculty teaching preparedness and leadership readiness were measured by an electronic questionnaire devised by the author and contributors of this article. Descriptive statistics were conducted for outcomes.

Results:
Findings indicate noontime education using a menu approach of listed offerings and curricular themes spiraled was a feasible faculty development method for teaching preparedness and leadership readiness for new administrative roles. Specifically, faculty reported increased use of active learning strategies after attending the noontime educational series.

Conclusions:
Next steps include longitudinal follow-up with our faculty participants to measure retention and sustainability of our findings, as well as additional instructional strategies that we could incorporate into future educational sessions.
ACR–ASTRO Practice Parameter for the Performance of Stereotactic Body Radiation Therapy
Authors: Chao Samuel T. , Dad Luqman K. , Dawson Laura A. , Desai Neil B. , Pacella Matthew , Rengan Ramesh , Xiao Ying , Yenice Kamil M. , Rosenthal Seth A. , Hartford Alan 
Published: May 2020

Aim/Objectives/Background:
To standardize the practice of stereotactic body radiation therapy (SBRT), the American College of Radiology (ACR) and the American Society for Radiation Oncology (ASTRO) cooperatively developed the practice parameter for SBRT. SBRT is a treatment technique that delivers radiation dose to a well-defined extracranial target in 5 fractions or less and usually employs a higher dose per fraction than used in conventional radiation.

Methods:
The ACR–ASTRO Practice Parameter for the Performance of Stereotactic Body Radiation Therapy was revised according to the process described on the ACR website (“The Process for Developing ACR Practice Parameters and Technical Standards,” www.acr.org/ClinicalResources/Practice-Parameters-and-Technical-Standards) by the Committee on Practice Parameters of the ACR Commission on Radiation Oncology in collaboration with the ASTRO. Both societies then reviewed and approved the document.

Results:
Given the complexities of SBRT, a separate document was created to develop a technical standard for the medical physics of SBRT (ACR–AAPM Technical Standard for Medical Physics Performance Monitoring of Stereotactic Body Radiation Therapy). Workflow, qualifications and responsibilities of personnel, specifications, documentation, quality control/safety/improvement, simulation/treatment, and follow-up were addressed in this practice parameter.

Conclusions:
This practice parameter assists practitioners in providing safe and appropriate SBRT treatment and care for patients when clinically indicated. As technologies and techniques continue to evolve, this document will be reviewed, revised and renewed accordingly to a 5 year or sooner timeline specified by the ACR.
VISUAL IMPAIRMENT AND MACULAR VASCULAR REMODELING SECONDARY TO RETROGRADE MACULOPATHY IN RETINAL DETACHMENT TREATED WITH SILICON OIL TAMPONADE
Authors: Dormegny Lea , Jeanjean Ludovic C. , Liu Xuanli , Messerlin Arnaud , Bourcier Tristan , Sauer Arnaud , Speeg-Schatz Claude , Gaucher David 
Published: May 2020

Purpose:
To assess the frequency of macular cysts (MCs) in retinal detachment treated with silicone oil and evaluate their impact on visual acuity and macular vascularization using optical coherence tomography-angiography.

Methods:
Forty-three eyes of 41 patients treated with silicone oil for retinal detachment were retrospectively studied. Best-corrected visual acuity and 6- × 6-mm optical coherence tomography-angiography examination at least 3 months after silicone oil removal were reviewed. In eyes with MCs, cyst area was measured on the en face optical coherence tomography-angiography image using ImageJ. Density of superficial capillary plexus and area of superficial foveal avascular zone were generated by the optical coherence tomography-angiography. Density of deep capillary plexus and deep foveal avascular zone area were measured using ImageJ.

Results:
Twenty-five eyes (58%) presented with MCs. Cysts were exclusively located in the inner nuclear layer in 60% of cases. Mean best-corrected visual acuity in the MC group was lower than that of the non-MC group (P = 0.012). Macular cyst area negatively correlated with best-corrected visual acuity (P = 0.0201). Density of superficial capillary plexus was higher in the MC group (P < 0.0001), whereas area of superficial foveal avascular zone was lower (P < 0.0001). Macular cyst area negatively correlated with density of deep capillary plexus (P < 0.001).

Conclusion:
The incidence of INL-MCs after silicone oil removal is high. These are associated with impaired vision and macular vascular remodeling. We highlight their similarity with the “retrograde maculopathy” phenomenon.
Self-Made Sleeve for Chandelier Light Simulation
Authors: Kruger Michael , Sommer Michael , Singer Christoph , Seidel Gerald 
Published: May 2020

Purpose:
To develop a quick and cost-effective alternative to a chandelier light for vitrectomy.

Methods:
The surgical material available in an ophthalmologic operating room was used to create a sleeve for the vitrectomy light probe and tested on 30 consecutive retinal detachment cases for feasibility.

Results:
A 64 × 5-mm cotton swab stick was cut into the length of the light probe minus the length of the trocar and subsequently pierced by a blunt needle. With this sleeve, the light probe could be safely handled similar to a chandelier light during surgery.

Conclusion:
A sleeve for the light probe can serve as a substitute for a chandelier light during scleral depression in retinal detachment surgery.
Indirect Impact of Ten-valent Pneumococcal Conjugate Vaccine Program on Reducing Antimicrobial Use and Tympanostomy Tube Placements in Finland
Authors: Palmu Arto A. , Rinta-Kokko Hanna , Nohynek Hanna , Nuorti J. Pekka 
Published: May 2020

Background:
Acute otitis media (AOM) is the most common reason for antimicrobial use, and tympanostomy tube placement (TTP) is the most common reason for surgery requiring general anesthesia in children. Ten-valent pneumococcal conjugate vaccine (PCV10) was introduced in Finland in 2010 for infants. We evaluated the indirect impact of PCV10 on these surrogate otitis outcomes in unvaccinated children.

Methods:
Using before-after design, unvaccinated children ineligible for National Vaccination Program (born January 2006 to May 2010) were followed-up during 2012–2016 (target cohort, age 1.5–7 years). The target cohort was compared with an age- and season-matched unvaccinated reference cohort (born January 2000 to May 2004) during 2006–2010. Antimicrobial purchase data were obtained from the Social Insurance Institution of Finland benefits register. We assessed the relative reduction by generalized Cox regression for outpatient purchases of antibiotics recommended for treatment of AOM in the Finnish guidelines. Data on all TTP procedures were obtained from national hospital discharge register and Social Insurance Institution benefits register.

Results:
The rate of outpatient purchases of antimicrobials recommended for AOM was 51 in the unvaccinated reference cohort and 44/100 person-years in the unvaccinated target cohort; relative rate reduction was 14.7% [95% confidence interval: 14.0–15.3] and absolute rate reduction 7/100 person-years. The rates of TTP in the reference and target cohorts were 1.66/100 and 1.61/100 person-years, respectively. The relative rate reduction was 3.6% (0.7–6.5).

Conclusions:
Antimicrobial use and TTP procedures reduced in unvaccinated children after PCV10 introduction in infants. These indirect effects contribute to the savings in health care resource use for otitis and may also help in combating antimicrobial resistance.
Cat-scratch Disease in the Pediatric Population
Authors: Sandoval Alejandra C. , Reyes Felipe T. , Prado María A. , Peña Anamaría L. , Viviani Tamara N. 
Published: May 2020

Background:

Bartonella henselae is the etiologic agent of cat-scratch disease, which affects the entire world population. Due to how poorly characterized the child population is, the objective was to describe the clinical behavior of this disease in children younger than 16 years of age.

Methods:
This was a descriptive study with prospective follow-up of all children younger than 16 years with clinical and serologic diagnoses between 2013 and 2018.

Results:
There were 142 patients; of these, 55.6% had localized disease, 34.5% disseminated with hepatosplenic involvement and 9.8% had atypical disease. The cases of atypical disease were prolonged febrile illness, Parinaud syndrome, subacute bacterial endocarditis/glomerulonephritis and aseptic meningitis. Cervical lymphadenopathy was the most frequent, followed by inguinal adenopathy. There were no differences between the type of manifestation and laboratory values except for a higher erythrocyte sedimentation rate tendency in patients with disseminated and/or atypical disease. The serologic titers throughout were distributed as follows: titer of 1/1024, 71.7%; titer of 1/512, 10.4% and titer of 1/256, 17.9%.

Conclusions:
This is, to our knowledge, the largest series of cat-scratch disease published. We demonstrate that in our environment, the inguinal location is suggestive of this disease, the disseminated presentation, frequent, and that the titers are probably much higher than in other populations, which perhaps indicates the need to re-examine the cut-off point for positivity.
Immunogenicity and Safety of an MF59-adjuvanted Quadrivalent Seasonal Influenza Vaccine in Young Children at High Risk of Influenza-associated Complications: A Phase III, Randomized, Observer-blind, Multicenter Clinical Trial
Authors: Esposito Susanna , Fling John , Chokephaibulkit Kulkanya , de Bruijn Marianne , Oberye Janine , Zhang Bin , Vossen Jeanique , Heijnen Esther , Smolenov Igor 
Published: May 2020

Background:
Vaccination against seasonal influenza is recommended for all children with a history of medical conditions placing them at increased risk of influenza-associated complications. The immunogenicity and efficacy of conventional influenza vaccines among young children are suboptimal; one strategy to enhance these is adjuvantation. We present immunogenicity and safety data for an MF59-adjuvanted quadrivalent influenza vaccine (aIIV4) in healthy children and those at a high risk of influenza-associated complications, based on the results of a recently completed phase III study.

Methods:
Children 6 months to 5 years of age (N = 10,644) were enrolled. The study was conducted across northern hemisphere seasons 2013–2014 and 2014–2015. Subjects received either aIIV4 or a nonadjuvanted comparator influenza vaccine. Antibody responses were assessed by hemagglutination inhibition assay against vaccine and heterologous strains. Long-term antibody persistence was assessed (ClinicalTrials.gov: NCT01964989).

Results:
aIIV4 induced significantly higher antibody titers than nonadjuvanted vaccine in high-risk subjects. aIIV4 antibody responses were of similar magnitude in high-risk and healthy subjects. Incidence of solicited local and systemic adverse events (AEs) was slightly higher in aIIV4 than nonadjuvanted vaccinees, in both the healthy and high-risk groups. Incidence of unsolicited AEs, serious AEs and AEs of special interest were similar for adjuvanted and nonadjuvanted vaccinees in the healthy and high-risk groups.

Conclusion:
aIIV4 was more immunogenic than nonadjuvanted vaccine in both the healthy and high-risk study groups. The reactogenicity and safety profiles of aIIV4 and the nonadjuvanted vaccine were acceptable and similar in 6-month- to 5-year-old high-risk and healthy children.
Complete Draft Genome Sequence of Cutibacterium (Propionibacterium) acnes Type Strain ATCC6919
Authors: Tang Hui-Jing , Si Kai-Wei , Zhang Xiao , Zhu He-Ling , Zheng Wen-Liang , Zhang Xi-Bao , Liang Jing-Yao , Ruan Jian-Bo 
Published: May 2020

Abstract

Objectives:
The wide use of antibiotics for acne is the main cause of drug-resistant Cutibacterium acnes. However, the complete genetic sequence reference of C. acnes has not yet been reported. Herein, we report the complete genetic sequence of Cutibacterium acnes type strain ATCC6919.

Methods:
Whole-genome sequencing of Cutibacterium acnes ATCC6919 was performed using both the Illumina Hiseq4000 and PacBio RSII single-molecule real-time sequencing platforms. The generated sequence reads were de novo assembled using the HGAP3 protocol of single-molecule real-time analysis v.2.3.0 software. The draft genome was annotated and further analyzed by various bioinformatics tools.

Results:
The total genome length of Cutibacterium acnes ATCC6919 was 2,495,001 bp (60.02% G + C content), with 2,450 coding sequences including 2,358 proteins, 45 tRNAs, 9 rRNAs, and 1 sRNA. The Comprehensive Antibiotic Resistance Database showed that the gene (thy A) found in ATCC6919 was associated with resistance to aminosalicylic acid. Antimicrobial susceptibility testing showed that this isolate was not sensitive to metronidazole and sulfamethoxazole, but was sensitive to all other tested antimicrobials (erythromycin, azithromycin, clarithromycin, tetracycline, minocycline, trimethoprim, levofloxacin, ceftriaxone, and doxycycline).

Conclusion:
This study reports the complete genome sequence of Cutibacterium acnes ATCC6919, which provides a valuable reference for comparative analysis based on the genomic characteristics and resistance gene diversity of Cutibacterium acnes.
Trends in Work-Related Musculoskeletal Disorders From the 2002 to 2014 General Social Survey, Quality of Work Life Supplement
Authors: Dick Robert B. , Lowe Brian D. , Lu Ming-Lun , Krieg Edward F. 
Published: May 2020

Objective:To update trends in prevalence of back and upper limb musculoskeletal symptoms and risk factors from the 2014 Quality of Work Life (QWL) Survey.Methods:Quadrennial QWL Surveys, 2002 to 2014 (withN = 1455, 1537, 1019, and 1124 in 2002, 2006, 2010, and 2014 surveys respectively) were analyzed for reports of back pain and pain in arms.Results:In the fourth analysis of this survey, 12-year trends continue to show a decline in back pain and pain in arms. Key physical (heavy lifting, hand movements, very hard physical effort) and psychosocial/work organizational factors (low supervisor support, work is always stressful, not enough time to get work done) remain associated with back and arm pain, with the physical risk factors showing the strongest associations.Conclusion:Physical exposure risk factors continue to be strongly associated with low back and arm pain and should be the focus of intervention strategies.