bluuebunny/crossref_metadata_2025 huggingface dataset:
The Bgee suite: integrated curated expression atlas and comparative transcriptomics in animals
Authors: Bastian Frederic B , Roux Julien , Niknejad Anne , Comte Aurélie , Fonseca Costa Sara S , de Farias Tarcisio Mendes , Moretti Sébastien , Parmentier Gilles , de Laval Valentine Rech , Rosikiewicz Marta , Wollbrett Julien , Echchiki Amina , Escoriza Angélique , Gharib Walid H , Gonzales-Porta Mar , Jarosz Yohan , Laurenczy Balazs , Moret Philippe , Person Emilie , Roelli Patrick , Sanjeev Komal , Seppey Mathieu , Robinson-Rechavi Marc
Published: September 2020

Bgee is a database to retrieve and compare gene expression patterns in multiple animal species, produced by integrating multiple data types (RNA-Seq, Affymetrix, in situ hybridization, and EST data). It is based exclusively on curated healthy wild-type expression data (e.g., no gene knock-out, no treatment, no disease), to provide a comparable reference of normal gene expression. Curation includes very large datasets such as GTEx (re-annotation of samples as ‘healthy’ or not) as well as many small ones. Data are integrated and made comparable between species thanks to consistent data annotation and processing, and to calls of presence/absence of expression, along with expression scores. As a result, Bgee is capable of detecting the conditions of expression of any single gene, accommodating any data type and species. Bgee provides several tools for analyses, allowing, e.g., automated comparisons of gene expression patterns within and between species, retrieval of the prefered conditions of expression of any gene, or enrichment analyses of conditions with expression of sets of genes. Bgee release 14.1 includes 29 animal species, and is available at https://bgee.org/ and through its Bioconductor R package BgeeDB.
Structural basis of the XPB helicase–Bax1 nuclease complex interacting with the repair bubble DNA
Authors: He Feng , DuPrez Kevin , Hilario Eduardo , Chen Zhenhang , Fan Li
Published: September 2020

Nucleotide excision repair (NER) removes various DNA lesions caused by UV light and chemical carcinogens. The DNA helicase XPB plays a key role in DNA opening and coordinating damage incision by nucleases during NER, but the underlying mechanisms remain unclear. Here, we report crystal structures of XPB from Sulfurisphaera tokodaii (St) bound to the nuclease Bax1 and their complex with a bubble DNA having one arm unwound in the crystal. StXPB and Bax1 together spirally encircle 10 base pairs of duplex DNA at the double-/single-stranded (ds–ss) junction. Furthermore, StXPB has its ThM motif intruding between the two DNA strands and gripping the 3′-overhang while Bax1 interacts with the 5′-overhang. This ternary complex likely reflects the state of repair bubble extension by the XPB and nuclease machine. ATP binding and hydrolysis by StXPB could lead to a spiral translocation along dsDNA and DNA strand separation by the ThM motif, revealing an unconventional DNA unwinding mechanism. Interestingly, the DNA is kept away from the nuclease domain of Bax1, potentially preventing DNA incision by Bax1 during repair bubble extension.
OptimalTTF-1: Enhancing tumor treating fields therapy with skull remodeling surgery. A clinical phase I trial in adult recurrent glioblastoma
Authors: Korshoej Anders Rosendal , Lukacova Slavka , Lassen-Ramshad Yasmin , Rahbek Christian , Severinsen Kåre Eg , Guldberg Trine Lignell , Mikic Nikola , Jensen Mette Haldrup , Cortnum Søren Ole Stigaard , von Oettingen Gorm , Sørensen Jens Christian Hedemann
Published: September 2020

Background

Preclinical studies suggest that skull remodeling surgery (SR-surgery) increases the dose of tumor treating fields (TTFields) in glioblastoma (GBM) and prevents wasteful current shunting through the skin. SR-surgery introduces minor skull defects to focus the cancer-inhibiting currents toward the tumor and increase the treatment dose. This study aimed to test the safety and feasibility of this concept in a phase I setting.

Methods

Fifteen adult patients with the first recurrence of GBM were treated with personalized SR-surgery, TTFields, and physician’s choice oncological therapy. The primary endpoint was toxicity and secondary endpoints included standard efficacy outcomes.

Results

SR-surgery resulted in a mean skull defect area of 10.6 cm2 producing a median TTFields enhancement of 32% (range 25–59%). The median TTFields treatment duration was 6.8 months and the median compliance rate 90%. Patients received either bevacizumab, bevacizumab/irinotecan, or temozolomide rechallenge. We observed 71 adverse events (AEs) of grades 1 (52%), 2 (35%), and 3 (13%). There were no grade 4 or 5 AEs or intervention-related serious AEs. Six patients experienced minor TTFields-induced skin rash. The median progression-free survival (PFS) was 4.6 months and the PFS rate at 6 months was 36%. The median overall survival (OS) was 15.5 months and the OS rate at 12 months was 55%.

Conclusions

TTFields therapy combined with SR-surgery and medical oncological treatment is safe and nontoxic and holds the potential to improve the outcome for GBM patients through focal dose enhancement in the tumor.
Normal Respiratory Flora as a Cause of Community-Acquired Pneumonia
Authors: Musher Daniel M , Jesudasen Sirus J , Barwatt Joseph W , Cohen Daniel N , Moss Benjamin J , Rodriguez-Barradas Maria C
Published: September 2020

Background

Intensive studies have failed to identify an etiologic agent in >50% cases of community-acquired pneumonia (CAP). Bacterial pneumonia follows aspiration of recognized bacterial pathogens (RBPs) such as Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus after they have colonize the nasopharynx. We hypothesized that aspiration of normal respiratory flora (NRF) might also cause CAP.

Methods

We studied 120 patients hospitalized for CAP who provided a high-quality sputum specimen at, or soon after admission, using Gram stain, quantitative sputum culture, bacterial speciation by matrix-assisted laser desorption ionization time-of-flight, and viral polymerase chain reaction. Thresholds for diagnosis of bacterial infection were ≥105 colony-forming units (cfu)/mL sputum for RBPs and ≥106 cfu for NRF.

Results

Recognized bacterial pathogens were found in 68 of 120 (56.7%) patients; 14 (20.1%) of these had a coinfecting respiratory virus. Normal respiratory flora were found in 31 (25.8%) patients; 10 (32.2%) had a coinfecting respiratory virus. Infection by ≥2 RBPs occurred in 10 cases and by NRF together with RBPs in 13 cases. Among NRF, organisms identified as Streptococcus mitis, which share many genetic features of S pneumoniae, predominated. A respiratory virus alone was found in 16 of 120 (13.3%) patients. Overall, an etiologic diagnosis was established in 95.8% of cases.

Conclusions

Normal respiratory flora, with or without viral coinfection, appear to have caused one quarter of cases of CAP and may have played a contributory role in an additional 10.8% of cases caused by RBPs. An etiology for CAP was identified in >95% of patients who provided a high-quality sputum at, or soon after, the time of admission.
Ralstonia solanacearum Type III Effector RipAC Targets SGT1 to Suppress Effector-Triggered Immunity
Authors: Nakano Masahito , Ichinose Yuki , Mukaihara Takafumi
Published: September 2020

Ralstonia solanacearum injects type III effectors into host cells to cause bacterial wilt in Solanaceae plants. To identify R. solanacearum effectors that suppress effector-triggered immunity (ETI) in plants, we evaluated R. solanacearum RS1000 effectors for their ability to suppress a hypersensitive response (HR) induced by the avirulence (Avr) effector RipAA in Nicotiana benthamiana. Out of the 11 effectors tested, 4 suppressed RipAA-triggered HR cell death. Among them, RipAC contains tandem repeats of the leucine-rich repeat (LRR) motif, which serves as the structural scaffold for a protein–protein interaction. We found that the LRR domain of RipAC was indispensable for the suppression of HR cell death during the recognition of RipAA and another Avr effector RipP1. By yeast two-hybrid screening, we identified N. benthamiana SGT1, an adaptor protein that forms a molecular chaperone complex with RAR1, as a host factor of the RipAC target. RipAC interacted with NbSGT1 in yeast and plant cells. Upon the formation of the molecular chaperone complex, the presence of RipAC markedly inhibits the interaction between NbSGT1 and NbRAR1. The RipAA- and RipP1-triggered HR cell deaths were not observed in NbSGT1-silenced plants. The introduction of RipAC was complementary to the reduced growth of the R. solanacearum mutant strain in N. benthamiana. These findings indicate that R. solanacearum uses RipAC to subvert the NbSGT1-mediated formation of the molecular chaperone complex and suppress ETI responses during the recognition of Avr effectors.
Anti-$\mathcal{PT}$ symmetry for a non-Hermitian Hamiltonian
Authors: Maamache Mustapha , Kheniche Linda
Published: September 2020

Anti-$\mathcal{PT}$ symmetry, $(\mathcal{PT})H=-H(\mathcal{PT})$, is a plausible variant of $\mathcal{PT}$ symmetry. Of particular interest is the situation when all the eigenstates of an anti-$\mathcal{PT}$-symmetric non-Hermitian Hamiltonian $H$ are also eigenstates of the $\mathcal{PT}$ operator; then, the quasi-energies are purely imaginary, which implies that the Hermitian conjugate $H^{+}=-H$, and thus they are connected via the relation $(\mathcal{PT})H=H^{+}\mathcal{PT}$, similar to the quasi-Hermiticity relation. Therefore, the eigenfunctions of the anti-$\mathcal{PT}$-symmetric $H$ form a complete orthonormal set with positive definite norms, and moreover the time evolution is unitary.
STUDY OF POLONIUM-210 IN PERSIAN CIGARETTE AND TOBACCO CROPS
Authors: Ghanbar-Moghaddam Behnaz , Fathivand Aliasghar
Published: September 2020

Alpha radiation from Polonium-210 (210Po) is considered to be an important agent of bronchial cancer in smokers. Besides reexamination of the radionuclide in domestic and imported cigarette brands separately, the radioactive contamination was also followed during the cigarette-producing procedure in Gilan as one of the major regions of tobacco cultivation in Iran. The activity level of 210Po in Iranian domestic and imported cigarettes averaged 38.4 ± 6% and 20.0 ± 7% mBq g−1, respectively. Drying in direct contact with fumes of fossil fuel seems like one of the main excessive sources of 210Po in Persian cigarettes.
The hyperopia of wealth: the cultural legitimation of economic inequalities by top earners
Authors: Kuusela Hanna
Published: September 2020

The article explores the attitudes and perceptions of those at the top of the income scale toward economic inequalities. Through a qualitative case study, it presents how a group of top 0.1% of earners in Finland—one of the most equal countries in the world—perceive and legitimize economic disparities in an era of rising inequalities. By drawing together studies of economic inequality with the sociology of elites, the article analyzes the cultural repertoires through which the top earners make sense of inequality. As its key finding, it introduces the concept of hyperopia of wealth to describe the discursive blindness that the wealthy respondents have toward the structural conditions of economic disparities. The results indicate that top earners have a tendency to either ignore or approve the existing inequalities while disregarding the role of the wealthy and wealth in the dynamics. This blindness is named as hyperopia of wealth, analogous to a condition in which one cannot see things that are close clearly.
A scalable method of determining physiological endotypes of sleep apnea from a polysomnographic sleep study
Authors: Finnsson Eysteinn , Ólafsdóttir Guðrún H , Loftsdóttir Dagmar L , Jónsson Sigurður Æ , Helgadóttir Halla , Ágústsson Jón S , Sands Scott A , Wellman Andrew
Published: September 2020

Sleep apnea is caused by several endophenotypic traits, namely pharyngeal collapsibility, poor muscle compensation, ventilatory instability (high loop gain), and arousability from sleep (low arousal threshold). Measures of these traits have shown promise for predicting outcomes of therapies (e.g. oral appliances, surgery, hypoglossal nerve stimulation, CPAP, and pharmaceuticals), which may become an integral part of precision sleep medicine. Currently, the methods Sands et al. developed for endotyping sleep apnea from polysomnography (PSG) are embedded in the original authors’ code, which is computationally expensive and requires technological expertise to run. We present a reimplementation and validation of the integrity of the original authors’ code by reproducing the endo-Phenotyping Using Polysomnography (PUP) method of Sands et al. The original MATLAB methods were reprogrammed in Python; efficient algorithms were developed to detect breaths, calculate normalized ventilation (moving time-average), and model ventilatory drive (intended ventilation). The new implementation (PUPpy) was validated by comparing the endotypes from PUPpy with the original PUP results. Both endotyping methods were applied to 38 manually scored polysomnographic studies. Results of the new implementation were strongly correlated with the original (p < 10–6 for all): ventilation at eupnea V̇ passive (ICC = 0.97), ventilation at arousal onset V̇ active (ICC = 0.97), loop gain (ICC = 0.96), and arousal threshold (ICC = 0.90). We successfully implemented the original PUP method by Sands et al. providing further evidence of its integrity. Additionally, we created a cloud-based version for scaling up sleep apnea endotyping that can be used more easily by a wider audience of researchers and clinicians.
Are age and sex effects on sleep slow waves only a matter of electroencephalogram amplitude?
Authors: Rosinvil Thaïna , Bouvier Justin , Dubé Jonathan , Lafrenière Alexandre , Bouchard Maude , Cyr-Cronier Jessica , Gosselin Nadia , Carrier Julie , Lina Jean-Marc
Published: September 2020

Aging is associated with reduced slow wave (SW) density (number SW/min in nonrapid-eye movement sleep) and amplitude. It has been proposed that an age-related decrease in SW density may be due to a reduction in electroencephalogram (EEG) amplitude instead of a decline in the capacity to generate SW. Here, we propose a data-driven approach to adapt SW amplitude criteria to age and sex. We predicted that the adapted criteria would reduce age and sex differences in SW density and SW characteristics but would not abolish them. A total of 284 healthy younger and older adults participated in one night of sleep EEG recording. We defined age- and sex-adapted SW criteria in a first cohort of younger (n = 97) and older (n = 110) individuals using a signal-to-noise ratio approach. We then used these age- and sex-specific criteria in an independent second cohort (n = 77, 38 younger and 39 older adults) to evaluate age and sex differences on SW density and SW characteristics. After adapting SW amplitude criteria, we showed maintenance of an age-related difference for SW density whereas the sex-related difference vanished. Indeed, older adults produced less SW compared with younger adults. Specifically, the adapted SW amplitude criteria increased the probability of occurrence of low amplitude SW (<80 µV) for older men especially. Our results thereby confirm an age-related decline in SW generation rather than an artifact in the detection amplitude criteria. As for the SW characteristics, the age- and sex-adapted criteria display reproducible effects across the two independent cohorts suggesting a more reliable inventory of the SW.
Multi-jurisdictional strategies and the choice of family wealth preservation structure and jurisdiction
Authors: Meyer Christo W
Published: September 2020

In today’s world, it is common to hear about individuals investing in multiple counties and businesses involved with cross-border transactions, and it is imperative that these businesses and stakeholders understand their global exposure and create a plan that maximises the benefit of this globally, while reducing costs, confusion, and stress. With the world becoming smaller because of this, more and more clients find themselves in a place, some without even realising it, where more advanced Multi-jurisdictional Planning and structuring is needed. It is not as easy as it sounds—first you will have to identify how to go about it, then where to start, in which countries to do it, and what structures to use.
Population structure of Cydia pomonella granulovirus isolates revealed by quantitative analysis of genetic variation
Authors: Fan Jiangbin , Jehle Johannes A , Wennmann Jörg T
Published: September 2020

Genetic diversity of viruses is driven by genomic mutations and selection through its host, resulting in differences in virulence as well as host responses. For baculoviruses, which are naturally occurring pathogens of insects and which are frequently sprayed on hundred thousands to millions of hectares as biocontrol agents of insect pests, the phenomenon of virus–host co-evolution is of particular scientific interest and economic importance because high virulence of baculovirus products is essential and emergence of host resistance needs to be avoided as much as possible. In the present study, the population structure of twenty isolates of the Cydia pomonella granulovirus (CpGV), including twelve isolates from different geographic origins and eight commercial formulations, were studied on the basis of next-generation sequencing data and by analyzing the distribution of single nucleotide polymorphisms (SNPs). An entirely consensus sequence-free quantitative SNP analysis was applied for the identification of 753 variant SNP sites being specific for single as well as groups of CpGV isolates. Based on the quantitative SNP analysis, homogenous, heterogenous as well as mixed isolates were identified and their proportions of genotypes were deciphered, revealing a high genetic diversity of CpGV isolates from around the world. Based on hierarchical clustering on principal components (HCPC), six distinct isolate/group clusters were identified, representing the proposed main phylogenetic lineages of CpGV but comprising full genome information from virus mixtures. The relative location of different isolates in HCPC reflected the proportion of variable compositions of different genotypes. The established methods provide novel analysis tools to decipher the molecular complexity of genotype mixtures in baculovirus isolates, thus depicting the population structure of baculovirus isolates in a more adequate form than consensus based analyses.
Influence of Soybean Tissue and Oomicide Seed Treatments on Oomycete Isolation
Authors: Noel Zachary A. , McDuffee Dair , Chilvers Martin I.
Published: September 2020

Soybean seedlings are vulnerable to different oomycete pathogens. Seed treatments containing the two antioomycete (oomicide) chemicals, metalaxyl-M (mefenoxam) and ethaboxam, are used for protection against oomycete pathogens. This study aimed to evaluate the influence of these two oomicides on isolation probability of oomycetes from soybean taproot or lateral root sections. Soybean plants were collected between the first and third trifoliate growth stages from five Midwest field locations in 2016 and four of the same fields in 2017. Oomycetes were isolated from taproot and lateral root. In 2016, 369 isolation attempts were completed, resulting in 121 isolates from the taproot and 154 isolates from the lateral root. In 2017, 468 isolation attempts were completed, with 44 isolates from the taproot and 120 isolates from the lateral roots. In three of nine site-years, the probability of isolating an oomycete from a taproot or lateral root section was significantly different. Seed treatments containing a mixture of ethaboxam and metalaxyl significantly reduced the probability of oomycete isolation from lateral roots in Illinois in 2016 and 2017, but not in other locations, which may have been related to the heavy soil type (clay loam). Among the 439 isolates collected from the two years sampled, 24 oomycete species were identified, and community compositions differed depending on location and year. The five most abundant species were Pythium sylvaticum (28.9%), P. heterothallicum (14.3%), P. ultimum var. ultimum (11.8%), P. attrantheridium (7.9%), and P. irregulare (6.6%), which accounted for 61.7% of the isolates collected. Oomicide sensitivity to ethaboxam and mefenoxam was assessed for >300 isolates. There were large differences in ethaboxam sensitivity among oomycete species, with effective concentrations to reduce optical density at 600 nm by 50% compared with the nonamended control (EC50 values) ranging from <0.01 to >100 μg/ml and a median of 0.65 μg/ml. Isolates with insensitivity to ethaboxam (>12 μg/ml) belonged to the species P. torulosum and P. rostratifingens but were sensitive to mefenoxam. Oomicide sensitivity to mefenoxam ranged from <0.01 to 0.62 μg/ml with a median of 0.03 μg/ml. The mean EC50 value of the five most abundant species to ethaboxam ranged from 0.35 to 0.97 μg/ml of ethaboxam and from 0.02 to 0.04 μg/ml of mefenoxam. No shift in sensitivity to mefenoxam or ethaboxam was observed as a result of soybean seed treatment or year relative to the nontreated seed controls. In summary, this study contributed to the understanding of the composition of oomycete populations from different soybean root tissues, locations, years, and seed treatments. Finally, seed treatments containing mefenoxam or metalaxyl plus ethaboxam can be effective in reducing the probability of oomycete isolation from soybean roots.
Inhibition of melanoma by survivin-specific lymphocytes combined with CCL17 and granulocyte-macrophage colony-stimulating factor in a mouse syngeneic model
Authors: Huang Lan , Chen Guisi , Chen Ying , Wu Wanwen , Tao Changli , Shao Hongwei , Huang Shulin , Shen Han
Published: September 2020

As a new generation of treatment, tumor immunotherapy targeting tumor-associated antigens (TAA) has attracted widespread attention. The survivin antigen belongs to TAA. It is a key inhibitor of apoptosis and a key regulator of cell cycle progression; furthermore, it may be a candidate target for tumor therapy. In addition, studies have confirmed that granulocyte-macrophage colony-stimulating factor (GM-CSF) and CCL17 significantly affect local anti-tumor immunity in the tumor microenvironment. The mouse survivin gene was screened by BIMAS and SYFPEITHI to obtain the highest scored mouse survivin epitope peptide, which was synthesized into a peptide vaccine to immunize normal mice. Subsequently, spleen lymphocytes were isolated to induce survivin-specific cytotoxic T lymphocytes (CTL). Next, genetic engineering was used to construct the B16F10 cell line that stably expressed CCL17 and GM-CSF genes. A mouse melanoma model was used to observe the effects of the combination of the three on tumor volume and tumor weight. In-vitro survivin-specific CTL combined with CCL17 gene had a stronger inhibitory effect on B16F10 cells, while combined GM-CSF gene did not enhance the inhibitory effect of CTL on B16F10 cells. In-vivo experiments demonstrated that survivin-specific CTL combined with GM-CSF and CCL17 genes can inhibit the growth of mouse melanoma. HE staining and immunohistochemistry showed that the tumor had more necrotic cells and more infiltrating lymphocytes. The results showed that survivin-specific CTL combined with CCL17 and GM-CSF genes could inhibit tumor growth better.
Variables Affecting Basal Cell Carcinoma and Melanoma In Situ Excision Clearance: A Multi-institutional Retrospective Study
Authors: Sharma Ajay N. , Cohen Joel L. , Haupt Eric C. , Sarpa Hege G. , Martin Brent C.
Published: September 2020

BACKGROUND

The primary endpoint for surgical excision of skin cancer is the positive margin status. Tumor characteristics may explain much of this risk, but other important factors can include physician specialty.

OBJECTIVE

To determine the variables affecting the success of a basal cell carcinoma (BCC) or melanoma in situ (MIS) excision.

METHODS/MATERIALS

An 8-year, multicenter, retrospective study of 5,800 BCC or MIS excisions performed at 13 different Kaiser Permanente medical centers. The margin status was determined by searching final pathology diagnosis texts for phrases associated with positive margins.

RESULTS

An incomplete excision rate was found in 23% of all specimens (BCC—22%, MIS—25%). Per specialty, the proportion of specimens with positive tumor margins was 24% for dermatology, 26% for plastic surgery, 28% for otolaryngology, and 12% for general surgery. General surgeons most often excised large tumors and tumors from truncal regions, 2 variables conferring lower odds of an incomplete excision. For non-Mohs procedures, dermatologists were no different than otolaryngologists or plastic surgeons in performing an incomplete BCC or MIS excision in all multivariate models (all p > .05).

CONCLUSION

Intrinsic tumor characteristics may influence the success of achieving tumor-free resection margins more than the specialty of the provider.
Evaluation of Bayesian Forecasting Methods for Prediction of Tacrolimus Exposure Using Samples Taken on Two Occasions in Adult Kidney Transplant Recipients
Authors: Brooks Emily , Tett Susan E. , Isbel Nicole M. , McWhinney Brett , Staatz Christine E.
Published: September 2020

Background:

Bayesian forecasting-based limited sampling strategies (LSSs) for tacrolimus have not been evaluated for the prediction of subsequent tacrolimus exposure. This study examined the predictive performance of Bayesian forecasting programs/services for the estimation of future tacrolimus area under the curve (AUC) from 0 to 12 hours (AUC0–12) in kidney transplant recipients.

Methods:

Tacrolimus concentrations were measured in 20 adult kidney transplant recipients, 1 month post-transplant, on 2 occasions one week apart. Twelve samples were taken predose and 13 samples were taken postdose at the specified times on the first and second sampling occasions, respectively. The predicted AUC0–12 (AUCpredicted) was estimated using Bayesian forecasting programs/services and data from both sampling occasions for each patient and compared with the fully measured AUC0–12 (AUCmeasured) calculated using the linear trapezoidal rule on the second sampling occasion. The bias (median percentage prediction error [MPPE]) and imprecision (median absolute prediction error [MAPE]) were determined.

Results:

Three programs/services were evaluated using different LSSs (C0; C0, C1, C3; C0, C1, C2, C4; and all available concentrations). MPPE and MAPE for the prediction of fully measured AUC0–12 were <15% for each program/service (with the exclusion of when only C0 was used), when using estimated AUC from data on the same (second) occasion. The MPPE and MAPE for the prediction of a future fully measured AUC0–12 were <15% for 2 programs/services (and for the third when participants who had a tacrolimus dose change between sampling days were excluded), when the occasion 1-AUCpredicted, using C0, C1, and C3, was compared with the occasion 2-AUCmeasured.

Conclusions:

All 3 Bayesian forecasting programs/services evaluated had acceptable bias and imprecision for predicting a future AUC0–12, using tacrolimus concentrations at C0, C1, and C3, and could be used for the accurate prediction of tacrolimus exposure in adult kidney transplant recipients.
Metastatic breast cancer presenting as an epithelial defect
Authors: Kirschenbaum Malka Davina , Rigor Paulo , Nik Narieman A. , Oboh Aruoriwo
Published: September 2020

A 62-year-old woman was referred for evaluation of a nonhealing epithelial defect of the left eye. Examination also revealed left upper lid ptosis, cicatricial lagophthalmos, and palpable lid masses. With probing, the patient admitted to recent history of lobular carcinoma and remote history of ductal carcinoma of the breast. Imaging showed abnormal tissue in the left extraconal orbit involving the lacrimal gland. After orbitotomy and biopsy of the mass, pathology specimens returned consistent with metastatic carcinoma of the left orbit with breast as the site of the primary tumor. The patient completed palliative radiation therapy and chemotherapy. Amniotic membranes were placed to promote healing of the persistent epithelial defect with good response. Unfortunately, the patient died approximately 1 year after her initial presentation secondary to her oligometastatic disease. There is a wide spectrum of clinical manifestations associated with orbital metastasis. Careful consideration must be given to cancer patients with ophthalmologic complaints.
The Last Three Decades of Contact Dermatitis
Authors: Şenel Engin
Published: September 2020

Background

Contact dermatitis is a common inflammatory skin disease, and it affects approximately 20% of the adult population. Bibliometrics is a statistical analysis of academic literature in a certain field. Although bibliometric studies have been popular in recent years, the literature has limited number of bibliometric researches focusing on dermatology.

Objective

We aimed to perform the first bibliometric analysis of contact dermatitis literature.

Methods

All data of our study were obtained from the databases provided by Web of Science. We used the keywords “contact dermatitis,” “irritant contact dermatitis,” “allergic contact dermatitis,” “cutaneous allergy,” “occupational dermatitis,” and “patch test” for our search. All items published between 1988 and 2017 were included.

Results

A total of 37,283 documents were found. The most studied research areas were dermatology, immunology, and allergy (79.7%, 65.02%, and 58.6%, respectively). The peak year of contact dermatitis literature was 2011 with 1,782 items. The United States covered 24.77% of contact dermatitis literature with 9,237 documents. Germany, the United Kingdom, Japan, and France followed the United States (n= 4,121, 3,420, 2,870, and 2,627 items, respectively). Denmark was the most productive country, followed by Sweden, Finland, Switzerland, and Belgium.

Conclusion

Physicians from developing and least developed countries should be supported to perform novel bibliometric researches on contact dermatitis.
Rapidly Growing Nodule
Authors: Polster Hannah , Tollefson Christina , Jacob Sharon E.
Published: September 2020

Teledermatology is a term used to describe how dermatologic medical services are provided via telecommunication technology. This is a case of a rapidly growing skin nodule on sun-exposed skin in a patient with a long history of skin cancers.
Topical Oxymetazoline (Rhofade) in Rosacea
Authors: Nagrani Nicole K. , Gonzalez Adrianna M. , Zito Patrick M. , Glick Brad P. , Rubenstein Richard M.
Published: September 2020

By definition, a drug is a medicine or substance that exerts a physiologic effect on an organism. In dermatology, various medications and substances are utilized on a daily basis, ranging from topical treatments to anesthetics in micrographic surgery. The purpose of this section is to focus on some of the more common substances, specifically how they work, how they are utilized, and routine alternatives (if available). The mechanism of action, usage, and alternative options of the medication topical oxymetazoline are discussed.
Illness Identity in Adolescents With Celiac Disease
Authors: Meyer Sonya , Lamash Liron
Published: September 2020

Objectives:

The aim was to examine the reliability and validity of the Illness Identity Questionnaire (IIQ) among adolescents with celiac disease (CD), to describe their illness identity characteristics, and to examine relationships between illness identity and self‐reported participation in food‐related activities and quality of life.

Methods:

Adolescents with CD (n = 91) were recruited for this cross‐sectional study via social media interest groups. Participants completed online questionnaires: the IIQ, the CD Children's Activities Chart (CD‐Chart), and the Pediatric Quality of Life Inventory (PedsQL).

Results:

Internal reliability was established for IIQ items (α = 0.87) and for its 4 components (α = 0.75‐‐0.90). The positive components (acceptance, enrichment) significantly differed from the negative components (rejection, engulfment), t(90) = 11.45, P < 0.001, d = 1.98. Feelings were more positive (M = 3.48, SD = 0.67) than negative (M = 2.06, SD = 0.76). The total IIQ was positively associated with the CD‐Chart amount of activities (r = 0.30, P < 0.01) and enjoyment (r = 0.34, P < 0.001) and with the PedsQL social scale (r = 0.53, P < 0.001).

Conclusions:

The IIQ established acceptable reliability and validity. In all, the adolescents with CD exhibited an illness identity profile that was more positive and adaptive than negative. The IIQ can contribute to understanding the developmental status of illness identity during the critical transition process from adolescence to adulthood.
Spasticity Outpatient Evaluation via Telemedicine
Authors: Verduzco-Gutierrez Monica , Romanoski Natasha L. , Capizzi Allison N. , Reebye Rajiv N. , Kotteduwa Jayawarden Supun , Ketchum Nicholas C. , O’Dell Michael
Published: September 2020

The COVID-19 global pandemic has resulted in significant changes to delivery of care in the field of physiatry. Most prominently, in-person visits have fast tracked to virtual visits. As we are forced to quickly adopt this new technology for our doctor-patient interactions, many questions remain with regard to structuring telemedicine visits for optimal outcomes. Little has been written on virtual evaluations of patients with spasticity. The intent of this article was to provide a framework for conducting a virtual spasticity assessment via telemedicine. We will provide tips on how to conduct a person-centered virtual examination assessment and how to document goals related to the virtual assessment.
Postoperative Treatment of Intracranial Hypotension Venous Congestion–Associated Brain Injury With Zolpidem
Authors: Desmarais Lauren M. , Milleville Kristen A. , Wagner Amy K.
Published: September 2020

A previously independent 75-yr-old man developed postoperative intracranial hypotension–associated venous congestion after an elective T10-pelvis fusion, which was complicated by durotomy. Postoperative day 0 magnetic resonance imaging noted symmetric edema of the basal ganglia, thalami, and cerebellar cortex as well as smooth diffuse pachymeningeal enhancement and dural thickening, consistent with postoperative intracranial hypotension–associated venous congestion. On postoperative day 0, patient developed tonic clonic seizures, and on postoperative day 2, patient was unable to follow commands or blink to visual threat, able to track eyes to sound only, and spontaneously moved all limbs. Patient was started on zolpidem 2.5 mg on postoperative day 2, and 12 hrs later, he had significantly improved motor function, arousal, verbalization, and followed simple commands. After three doses, patient was fully alert and oriented with improved mobility and comprehension. Six zolpidem doses were administered in total, and repeat magnetic resonance imaging on postoperative day 16 showed markedly improved regional edema. The patient was admitted to a brain injury inpatient rehabilitation unit and was discharged to home 9 days later with Functional Independence Measure gain of 17. Intracranial hypotension can adversely affect primary mesocircuit structures supporting arousal. Zolpidem, a selective α-1-subunit GABA-A agonist, supports GABAergic tone in these regions. This patient’s clinical presentation and recovery paralleled selective basal ganglial-thalamic edema development and resolution.
Enemella gen. nov., Enemella evansiae sp. nov., Enemella dayhoffiae sp. nov. and Parenemella sanctibonifatiensis gen. nov., sp. nov., novel taxa assignable to the family Propionibacteriaceae and derived from human clinical samples
Authors: Bernard Kathryn A. , Burdz Tamara , Pacheco Ana Luisa , Wiebe Deborah , Patel Nisha B. , Lawson Paul A. , Domingo Marc-Christian , Longtin Jean , Bernier Anne-Marie
Published: September 2020

Nine Gram-stain-positive cocci, coccobacilli or short, rod-shaped strains recovered from clinical sources from patients located in two Canadian provinces and one environmental source were extensively studied. Clinical sources included blood cultures, cerebral spinal fluid, lymph node, lung biopsy and peritoneal fluid. Through 16S rRNA gene and whole genome sequencing analyses, the strains were found to cluster into three groups, closest to but distinguished from other genera in the family

Propionibacteriaceae

. The genomes from these bacteria had high G+C content, ranging from 67.8–69.56 mol%, and genome sizes of 3.02–4.52 Mb. Biochemical and chemotaxonomic properties including branched-chain cellular fatty acids, l-lysine diaminopimelic acid (ll-DAP) and cell-wall type A3γ (ll-DAP-gly) containing ll-DAP, alanine, glycine and glutamic acid were found and so the strains were therefore deemed to be consistent with other new genera in this family. Based on this investigation, we propose Enemella gen. nov., Enemella evansiae sp. nov., Enemella dayhoffiae sp. nov. and Parenemella sanctibonifatiensis gen. nov., sp. nov. for these taxa. Misidentified taxon ‘Ponticoccus gilvus’ was found to be assignable to Enemella evansiae based on this study.
Brevibacillus migulae sp. nov., isolated from a Yellow River sediment sample
Authors: Niu Mingming , Ming Hong , Cheng Li-jiao , Yi Bing-fang , Xia Ting-ting , Li Meng , Nie Guo-Xing
Published: September 2020

Strain CFH S0501T, a novel Gram-stain-positive, aerobic, rod-shaped, endospore-forming and motile micro-organism with peritrichous flagella, was isolated from a sediment sample collected from the Yellow River in Henan Province, PR China. Optimum growth was observed at 28 °C, pH 7.0 and without NaCl. Phylogenetic analysis based on the 16S rRNA gene sequences indicated that the strain belonged to the genus

Brevibacillus

and was closely related to

Brevibacillus centrosporus

DSM 8445T and

Brevibacillus ginsengisoli

Gsoil 3088T (with 96.8 and 96.7 % sequence similarity, respectively). The predominant menaquinone was MK-7. Major cellular fatty acids were anteiso-C15 : 0 and iso-C15 : 0. Polar lipids consisted of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylmonomethylethanolamine, phosphatidylethanolamine, two unidentified phospholipids and an unidentified polar lipid. The cell-wall peptidoglycan was found to contain meso-diaminopimelic acid. The genome size was 5.26 Mbp with a G+C content of 49.7 mol%. The average nucleotide identity (ANI) and in silico DNA–DNAhybridization (DDH) values between CFH S0501T and the other species of the genus

Brevibacillus

were found to be low (ANIm <86.11 %, ANIb <70.30 % and DDH <25.00 %). Based on physiological properties, chemotaxonomic characteristics and low ANI and DDH results, strain CFH S0501T is considered to represent a novel species, for which the name Brevibacillus migulae sp. nov. is proposed. The type strain is CFH S0501T (=DSM 29940T=BCRC 80809T).
Caldichromatium japonicum gen. nov., sp. nov., a novel thermophilic phototrophic purple sulphur bacterium of the Chromatiaceae isolated from Nakabusa hot springs, Japan
Authors: Saini Mohit Kumar , ChihChe Weng , Soulier Nathan , Sebastian Aswathy , Albert Istvan , Thiel Vera , Bryant Donald A. , Hanada Satoshi , Tank Marcus
Published: September 2020

A novel thermophilic phototrophic purple sulphur bacterium was isolated from microbial mats (56 °C) at Nakabusa hot springs, Nagano prefecture, Japan. Cells were motile, rod-shaped, stain Gram-negative and stored sulphur globules intracellularly. Bacteriochlorophyll a and carotenoids of the normal spirilloxanthin series were the major pigments. Dense liquid cultures were red in colour. Strain No.7T was able to grow photoautotrophically using sulfide, thiosulfate, sulfite and hydrogen (in the presence of sulfide) as electron donors and bicarbonate as the sole carbon source. Optimum growth occurred under anaerobic conditions in the light at 50 °C (range, 40–56 °C) and pH 7.2 (range, pH 7–8). Major fatty acids were C16 : 0 (46.8 %), C16 : 1 ω7c (19.9 %), C18 : 1 ω7c (21.1 %), C14 : 0 (4.6 %) and C18 : 0 (2.4 %). The polar lipid profile showed phosphatidylglycerol and unidentified aminophospholipids to be the major lipids. The only quinone detected was ubiquinone-8. 16S rRNA gene sequence comparisons indicated that the novel bacterium is only distantly related to

Thermochromatium tepidum

with a nucleotide identity of 90.4 %. The phylogenetic analysis supported the high novelty of strain No.7T with a long-branching phylogenetic position within the

Chromatiaceae

next to

Thermochromatium tepidum

. The genome comprised a circular chromosome of 2.99 Mbp (2 989 870 bp), included no plasmids and had a DNA G+C content of 61.2 mol%. Polyphasic taxonomic analyses of the isolate suggested strain No.7T is a novel genus within the

Chromatiaceae

. The proposed genus name of the second truly thermophilic purple sulphur bacterium is Caldichromatium gen. nov. with the type species Caldichromatium japonicum sp. nov. (DSM 110881=JCM 39101).
Non-permissive SARS-CoV-2 infection in human neurospheres
Authors: Pedrosa Carolina da S. G. , Goto-Silva Livia , Temerozo Jairo R. , Souza Leticia R. Q. , Vitória Gabriela , Ornelas Isis M. , Karmirian Karina , Mendes Mayara A. , Gomes Ismael C. , Sacramento Carolina Q. , Fintelman-Rodrigues Natalia , Soares Vinicius Cardoso , Gomes Dias Suelen da Silva , Salerno José Alexandre , Puig-Pijuan Teresa , Oliveira Julia T. , Aragão Luiz G. H. S. , Torquato Thayana C. Q. , Veríssimo Carla , Biagi Diogo , Cruvinel Estela M. , Dariolli Rafael , Furtado Daniel R. , Borges Helena L. , Bozza Patrícia T. , Rehen Stevens , Souza Thiago Moreno L. , Guimarães Marília Zaluar P.
Published: September 2020

Coronavirus disease 2019 (COVID-19) was initially described as a viral infection of the respiratory tract. It is now known, however, that several other organs are affected, including the brain. Neurological manifestations such as stroke, encephalitis, and psychiatric conditions have been reported in COVID-19 patients, but the neurotropic potential of the virus is still debated. Herein, we sought to investigate SARS-CoV-2 infection in human neural cells. We demonstrated that SARS-CoV-2 infection of neural tissue is non-permissive, however, it can elicit inflammatory response and cell damage. These findings add to the hypothesis that most of the neural damage caused by SARS-CoV-2 infection is due to a systemic inflammation leading to indirect harmful effects on the central nervous system despite the absence of local viral replication.
Variations in human monocyte-derived macrophage antimicrobial activities and their associations with tuberculosis clinical manifestations
Authors: Tram Trinh T. B. , Ha Vu T. N. , Thu Do D. A. , Dinh Tran D. , Nhung Hoang N. , Hanh Nguyen T. , Phu Nguyen H. , Thwaites Guy E. , Thuong Nguyen T. T.
Published: September 2020

Macrophages play a significant role in preventing infection through antimicrobial activities, particularly acidification and proteolysis. Mycobacterium tuberculosis infection can lead to diverse outcomes, from latent asymptomatic infection to active disease involving multiple organs. Monocyte-derived macrophage is one of the main cell types accumulating in lungs following Mtb infection. The variation of intracellular activities of monocyte-derived macrophages in humans and the influence of these activities on the tuberculosis (TB) spectrum are not well understood. By exploiting ligand-specific bead-based assays, we investigated macrophage antimicrobial activities real-time in healthy volunteers (n=53) with 35 cases of latent TB (LTB), and those with active TB (ATB) and either pulmonary TB (PTB, n=70) or TB meningitis (TBM, n=77). We found wide person-to-person variations in acidification and proteolytic activities in response to both non-immunogenic IgG and pathogenic ligands comprising trehalose 6,6′-dimycolate (TDM) from Mycobacterium tuberculosis or β-glucan from Saccharamyces cerevisiase. The variation in the macrophage activities remained similar regardless of stimuli; however, IgG induced stronger acidification activity than immunogenic ligands TDM (P=10−5, 3×10−5 and 0.01 at 30, 60 and 90 min) and β-glucan (P=10−4, 3×10−4 and 0.04 at 30, 60 and 90 min). Variation in proteolysis activity was slightly higher in LTB than in ATB (CV=40% in LTB vs. 29% in ATB, P=0.03). There was no difference in measured antimicrobial activities in response to TDM and bacterial killing in macrophages from LTB and ATB, or from PTB and TBM. Our results indicate that antimicrobial activities of monocyte-derived macrophages vary among individuals and show immunological dependence, but suggest these activities cannot be solely responsible for the control of bacterial replication or dissemination in TB.
Dorsolateral striatum engagement during reversal learning
Authors: Bergstrom Hadley C. , Lieberman Abby G. , Graybeal Carolyn , Lipkin Anna M. , Holmes Andrew
Published: September 2020

Most experimental preparations demonstrate a role for dorsolateral striatum (DLS) in stimulus-response, but not outcome-based, learning. Here, we assessed DLS involvement in a touchscreen-based reversal task requiring mice to update choice following a change in stimulus-reward contingencies. In vivo single-unit recordings in the DLS showed reversal produced a population-level shift from excited to inhibited neuronal activity prior to choices being made. The larger the shift, the faster mice reversed. Furthermore, optogenetic photosilencing DLS neurons during choice increased early reversal errors. These findings suggest dynamic DLS engagement may facilitate reversal, possibly by signaling a change in contingencies to other striatal and cortical regions.
Bidirectional regulation of distinct memory domains by α5-subunit-containing GABAAreceptors in CA1 pyramidal neurons
Authors: Engin Elif , Sigal Maksim , Benke Dietmar , Zeller Anja , Rudolph Uwe
Published: September 2020

Reduction in the expression or function of α5-subunit-containing GABAAreceptors (α5GABAARs) leads to improvement in several hippocampus-dependent memory domains. However, studies thus far mostly lack anatomical specificity in terms of neuronal circuits and populations. We demonstrate that mice with a selective knockdown of α5GABAARs in CA1 pyramidal neurons (α5CA1KO mice) show improved spatial and trace fear-conditioning memory. Unexpectedly, α5CA1KO mice were comparable to controls in contextual fear-conditioning but showed an impairment in context discrimination, suggesting fine-tuning of activity in CA1 pyramidal cell dendrites through α5-mediated inhibition might be necessary for distinguishing highly similar contexts.
Multiple crystal forms of human MacroD2
Authors: Wazir Sarah , Maksimainen Mirko M. , Lehtiö Lari
Published: September 2020

MacroD2 is one of the three human macrodomain proteins characterized by their protein-linked mono-ADP-ribosyl-hydrolyzing activity. MacroD2 is a single-domain protein that contains a deep ADP-ribose-binding groove. In this study, new crystallization conditions for MacroD2 were found and three crystal structures of human MacroD2 in the apo state were solved in space groupsP41212,P43212 andP43, and refined at 1.75, 1.90 and 1.70 Å resolution, respectively. Structural comparison of the apo crystal structures with the previously reported crystal structure of MacroD2 in complex with ADP-ribose revealed conformational changes in the side chains of Val101, Ile189 and Phe224 induced by the binding of ADP-ribose in the active site. These conformational variations may potentially facilitate design efforts of a MacroD2 inhibitor.