bluuebunny/crossref_metadata_2025 huggingface dataset:
Factors related to disagreement between self-reported versus objective measurement of allergen sensitization at a tertiary pediatric center in Beijing, China
Authors: Miao Qing , Xiang Li , Guan Hui , Liu Yongge , Li Zhen , Ren Yixin , Xu Wei
Published: May 2020

Background

The objectives of present study were to examine the level of disagreement between self-reported and objective measurement of sensitization to common inhalant allergens, and to explore the potential risk factors that might contribute to this discrepancy.

Methods

A total of 215 children were enrolled from pediatric clinics at a tertiary pediatric center in Beijing, China. A survey questionnaires regarding self-perceived sensitization was completed by participants’ parents/caregiver, meanwhile, skin prick testing(SPT) was performed as objective assessment of sensitization. Extent of agreement between self-reported versus SPT-measured sensitization to individual allergen was calculated using Cohen’s kappa (κ) coefficient. Multivariable regression analyses were used to determine the factors associated with discrepancy between self-reported and objective measurement of sensitization.

Results

119(55.3%) patients have reported to be sensitized to at least one of inhalant allergen, whereas 167(77.7%) patients had a positive skin testing response. Agreement between self-perceived and actual aeroallergen sensitization was moderate for mites(κ = 0.518) and grass pollen mix(κ = 0.451), moreover, fair agreement was observed for mold(κ = 0.316) and cockroach(κ = 0.297), respectively. There was a least agreement between perceived and actual sensitization observed for pet dander, with a kappa coefficient of 0.005. Subjects’ age, atopy history, ownership of pet may increase the risk of disagreement, moreover, background factors of informant, like: age, education level, and the relationship with enrolled subjects, were linked to the incidence of disagreement between self-reported sensitization in comparison with SPT results.

Conclusion

Questionnaire-based self-assessment is easy way to collect clinical information on allergen sensitization; however, the accuracy of questionnaire-derived information is more likely to be influenced by respondent’s background factors. The information from the questionnaire report is considered to be more reliable when in combination with objective assessment of sensitization, including blood IgE testing and SPT.
Conscious sedation for the management of dental anxiety in third molar extraction surgery: a systematic review
Authors: Melini Matteo , Forni Andrea , Cavallin Francesco , Parotto Matteo , Zanette Gastone
Published: May 2020

Background

Dental anxiety is a condition associated with avoidance of dental treatment and increased medical and surgical risks. This systematic review aims to summarize available evidence on conscious sedation techniques used for the management of Dental anxiety in patients scheduled for third molar extraction surgery, to identify best approaches and knowledge gaps.

Methods

A comprehensive search was conducted including MEDLINE/Pubmed, EMBASE, SCOPUS, clinicaltrials.gov and the Cochrane Database of Systematic Reviews through March 2019. Only randomized controlled trials were included. PRISMA guidelines were followed. Risk of bias was appraised as reported in the Cochrane Handbook for Systematic Reviews of Interventions.

Results

Seventeen RCTs with a total of 1788 patients were included. Some aspects limited the feasibility of a meaningful meta-analysis, thus a narrative synthesis was conducted. Conscious sedation was associated with improvement in Dental anxiety in six studies. One study reported lower cortisol levels with midazolam vs. placebo, while another study found significant variation in perioperative renin levels with remifentanil vs. placebo.

Conclusions

This review found inconclusive and conflicting findings about the role of Conscious sedation in managing Dental anxiety during third molar extraction surgery. Relevant questions remain unanswered due to the lack of consistent, standardized outcome measures. Future research may benefit from addressing these limitations in study design.
Pharyngeal metastasis following living-donor liver transplantation for hepatocellular carcinoma: a case report and literature review
Authors: Tohyama Taiji , Sakamoto Katsunori , Tamura Kei , Nakamura Taro , Watanabe Jota , Wakisaka Hiroyuki , Takada Yasutsugu
Published: May 2020

Background

The most common sites of recurrence after liver transplantation for hepatocellular carcinoma (HCC) have been reported to be the liver, lung, bone, and adrenal glands, but there have also been many reports of cases of multiple recurrence. The prognosis after recurrence is poor, with reported median survival after recurrence of HCC ranging from 9 to 19 months. Here, we report a case of long-term survival after recurrence of pharyngeal metastasis following living-donor liver transplantation (LDLT) for HCC within the Milan criteria, by resection of the metastatic region and cervical lymph node dissection.

Case presentation

A 47-year-old man with a Model End-stage Liver Disease (MELD) score of 11 underwent LDLT for HCC within the Milan criteria for liver cirrhosis associated with hepatitis B virus infection, with his 48-year-old elder brother as the living donor. One year and 10 months after liver transplantation, he visited a nearby hospital with a chief complaint of discomfort on swallowing. A pedunculated polyp was found in the hypopharynx, and biopsy revealed HCC metastasis. We performed pharyngeal polypectomy. Two years later, cervical lymph node metastasis appeared, and neck lymph node dissection was performed. Although recurrence subsequently occurred three times in the grafted liver, the patient is still alive 12 years and 10 months after recurrence of pharyngeal metastasis. He is now a tumor-free outpatient taking sorafenib.

Conclusion

It is necessary to recognize that the nasopharyngeal region is a potential site of HCC metastasis. Prognostic improvement can be expected with close follow-up, early detection, and multidisciplinary treatment, including radical resection.
Complement activating ABO anti-A IgM/IgG act synergistically to cause erythrophagocytosis: implications among minor ABO incompatible transfusions
Authors: Pandey Priyanka , Anani Waseem Q. , Pugh Tina , Gottschall Jerome L. , Denomme Gregory A.
Published: May 2020

Background

Typically minor ABO incompatible platelet products are transfused without any incident, yet serious hemolytic transfusion reactions occur. To mitigate these events, ABO ‘low titer’ products are used for minor ABO incompatible transfusions. We sought to understand the role of IgM/IgG and complement activation by anti-A on extravascular hemolysis.

Methods

Samples evaluated included (i) Group O plasma from a blood donor whose apheresis platelet product resulted in an extravascular transfusion reaction, (ii) Group O plasma from 12 healthy donors with matching titers that activated complement (N = 6) or not (N = 6), and (iii) Group O sera from 10 patients with anti-A hemolysin activity. A flow cytometric monocyte erythrophagocytosis assay was developed using monocytes isolated by immunomagnetic CD14-positive selection from ACD whole blood of healthy donors. Monocytes were frozen at − 80 °C in 10% dimethyl sulfoxide/FBS and then thawed/reconstituted on the day of use. Monocytes were co-incubated with anti-A-sensitized fluorescently-labeled Group A1 + RBCs with and without fresh Group A serum as a source of complement C3, and erythrophagocytosis was analyzed by flow cytometry. The dependency of IgM/IgG anti-A and complement C3 activation for RBC erythrophagocytosis was studied. Anti-A IgG subclass specificities were examined for specific samples.

Results

The plasma and sera had variable direct agglutinating (IgM) and indirect (IgG) titers. None of 12 selected samples showed monocyte-dependent erythrophagocytosis with or without complement activation. The donor sample causing a hemolytic transfusion reaction and 2 of the 10 patient sera with hemolysin activity showed significant erythrophagocytosis (> 10%) only when complement C3 was activated. The single donor plasma and two sera demonstrating significant erythrophagocytosis had high IgM (≥ 128) and IgG titers (> 1024). The donor plasma anti-A was IgG1, while the patient sera were an IgG3 and an IgG1 plus IgG2.

Conclusion

High anti-A IgM/IgG titers act synergistically to cause significant monocyte erythrophagocytosis by activating complement C3, thus engaging both Fcγ- and CR1-receptors.
Ultrafast dynamic contrast-enhanced breast MRI may generate prognostic imaging markers of breast cancer
Authors: Onishi Natsuko , Sadinski Meredith , Hughes Mary C. , Ko Eun Sook , Gibbs Peter , Gallagher Katherine M. , Fung Maggie M. , Hunt Theodore J. , Martinez Danny F. , Shukla-Dave Amita , Morris Elizabeth A. , Sutton Elizabeth J.
Published: May 2020

Background

Ultrafast dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI)-derived kinetic parameters have demonstrated at least equivalent accuracy to standard DCE-MRI in differentiating malignant from benign breast lesions. However, it is unclear if they have any efficacy as prognostic imaging markers. The aim of this study was to investigate the relationship between ultrafast DCE-MRI-derived kinetic parameters and breast cancer characteristics.

Methods

Consecutive breast MRI examinations between February 2017 and January 2018 were retrospectively reviewed to determine those examinations that meet the following inclusion criteria: (1) BI-RADS 4–6 MRI performed on a 3T scanner with a 16-channel breast coil and (2) a hybrid clinical protocol with 15 phases of ultrafast DCE-MRI (temporal resolution of 2.7–4.6 s) followed by early and delayed phases of standard DCE-MRI. The study included 125 examinations with 142 biopsy-proven breast cancer lesions. Ultrafast DCE-MRI-derived kinetic parameters (maximum slope [MS] and bolus arrival time [BAT]) were calculated for the entire volume of each lesion. Comparisons of these parameters between different cancer characteristics were made using generalized estimating equations, accounting for the presence of multiple lesions per patient. All comparisons were exploratory and adjustment for multiple comparisons was not performed; P values < 0.05 were considered statistically significant.

Results

Significantly larger MS and shorter BAT were observed for invasive carcinoma than ductal carcinoma in situ (DCIS) (P < 0.001 and P = 0.008, respectively). Significantly shorter BAT was observed for invasive carcinomas with more aggressive characteristics than those with less aggressive characteristics: grade 3 vs. grades 1–2 (P = 0.025), invasive ductal carcinoma vs. invasive lobular carcinoma (P = 0.002), and triple negative or HER2 type vs. luminal type (P < 0.001).

Conclusions

Ultrafast DCE-MRI-derived parameters showed a strong relationship with some breast cancer characteristics, especially histopathology and molecular subtype.
Longitudinal changes and determinants of parental willingness to pay for the prevention of childhood overweight and obesity
Authors: Lauer Romy , Traub Meike , Hansen Sylvia , Kilian Reinhold , Steinacker Jürgen Michael , Kesztyüs Dorothea
Published: May 2020

Background

Willingness to Pay (WTP) is an alternative to measure quality-adjusted life years for cost-effectiveness analyses. The aim was to evaluate longitudinal changes and determinants of parental WTP for the prevention of childhood overweight and obesity.

Methods

Longitudinal data from post- (T2) and follow-up (T3) measurements of a school-based health promotion program in Germany. Parental questionnaires included general WTP and the corresponding amount to reduce incidental childhood overweight and obesity by half. Longitudinal differences were examined with the McNemar test for general WTP and the Wilcoxon signed-rank test for the amount of WTP. Regression analyses were conducted to detect determinants.

Results

General parental WTP significantly decreased from 48.9% to 35.8% (p < 0.001, n = 760). Logistic regression analysis (n = 561) showed that parents with a tertiary education level and a positive general WTP at T2, families with a higher monthly household income, and those with abdominally obese children were significant predictors of general WTP at T3. Median amount of WTP at T3 was €20.00 (mean = €27.96 ± 26.90, n = 274). Assuming a WTP of €0 for those who were generally not willing to pay or did not answer, resulted in a median amount of WTP at T3 of €0 (m = €8.45, sd = €19.58, n = 906). According to linear regression analysis WTP at T2 was the only significant predictor for the amount of WTP at T3 (p = 0.000, n = 181).

Conclusions

Despite the decline of general WTP, these results are a reflection of the public awareness of the problem and the need for action. Policy makers should recognize this and initiate sustainable public preventive strategies.

Trial registration

DRKS, DRKS00000494. Registered 25 August 2010, https://www.drks.de/drks_web/.
ATP measurement as an objective method to measure environmental contamination in 9 hospitals in the Dutch/Belgian border area
Authors:   on behalf of the i-4-1-Health Study Group, van Arkel Andreas , Willemsen Ina , Kilsdonk-Bode Linda , Vlamings-Wagenaars Sindy , van Oudheusden Anne , Waegemaeker Pascal De , Leroux-Roels Isabel , Verelst Martine , Maas Evelien , van Oosten Anita , Willemse Patricia , van Asselen Esther , Klomp-Berens Ella , Franssen Karen , Van Cauwenberg Elise , Kluytmans Jan
Published: May 2020

Background

The objective of this study was to determine the level of environmental contamination in hospitals in the Dutch/Belgian border area, using ATP measurements.

Design

A cross-sectional observational survey.

Methods

Standardized ATP measurements were conducted in 9 hospitals on 32 hospital wards. Thirty pre-defined surfaces per hospital ward were measured with the 3 M Clean Trace NG luminometer. Results are displayed in relative light units (RLU). RLU > 1000 was considered as “not clean.” Differences in RLU values were compared between countries, hospitals, fomite groups and medical specialties.

Results

A total of 960 ATP measurements were performed, ranging from 60 up to 120 per hospital. The median RLU-value was 568 (range: 3–277,586) and 37.7% of the measurements were rated as not clean (RLU > 1000). There were significant differences between countries, hospitals and fomite groups.

Conclusion

ATP measurements can be used as a more objective approach to determine the level of environmental contamination in hospitals. Significant differences in ATP levels were found between hospitals and between countries. Also, substantial differences were found between different fomite groups. These findings offer potential targets for improvement of cleanliness in healthcare facilities.
Alterations of gut microbiome accelerate multiple myeloma progression by increasing the relative abundances of nitrogen-recycling bacteria
Authors: Jian Xingxing , Zhu Yinghong , Ouyang Jian , Wang Yihui , Lei Qian , Xia Jiliang , Guan Yongjun , Zhang Jingyu , Guo Jiaojiao , He Yanjuan , Wang Jinuo , Li Jian , Lin Jingchao , Su Mingming , Li Guancheng , Wu Minghua , Qiu Lugui , Xiang Juanjuan , Xie Lu , Jia Wei , Zhou Wen
Published: May 2020

Background

Gut microbiome alterations are closely related to human health and linked to a variety of diseases. Although great efforts have been made to understand the risk factors for multiple myeloma (MM), little is known about the role of the gut microbiome and alterations of its metabolic functions in the development of MM.

Results

Here, in a cohort of newly diagnosed patients with MM and healthy controls (HCs), significant differences in metagenomic composition were discovered, for the first time, with higher bacterial diversity in MM. Specifically, nitrogen-recycling bacteria such asKlebsiellaandStreptococcuswere significantly enriched in MM. Also, the bacteria enriched in MM were significantly correlated with the host metabolome, suggesting strong metabolic interactions between microbes and the host. In addition, the MM-enriched bacteria likely result from the regulation of urea nitrogen accumulated during MM progression. Furthermore, by performing fecal microbiota transplantation (FMT) into 5TGM1 mice, we proposed a mechanistic explanation for the interaction between MM-enriched bacteria and MM progression via recycling urea nitrogen. Further experiments validated thatKlebsiella pneumoniaepromoted MM progression via de novo synthesis of glutamine in mice and that the mice fed with glutamine-deficient diet exhibited slower MM progression.

Conclusions

Overall, our findings unveil a novel function of the altered gut microbiome in accelerating the malignant progression of MM and open new avenues for novel treatment strategies via manipulation of the intestinal microbiota of MM patients.
Rare metastatic pancreatic tumors from lung cancer with cystic changes resembling intraductal papillary mucinous neoplasm: a case report
Authors: Watanabe Akira , Harimoto Norifumi , Yamanaka Takahiro , Ishii Norihiro , Tsukagoshi Mariko , Igarashi Takamichi , Kubo Norio , Araki Kenichiro , Suzuki Aya , Hara Kenichiro , Shirabe Ken
Published: May 2020

Background

Metastatic pancreatic tumors from lung cancer (MPTLC) constitute 3% of all metastatic pancreatic tumors. We present an extremely rare case of cystic MPTLC that was difficult to distinguish from intraductal papillary mucinous neoplasm (IPMN).

Case presentation

The patient was a 74-year-old woman who underwent lobectomy of lung cancer 2 years before presentation to our hospital. She was referred to our department for resection of cystic pancreatic tumors, which were diagnosed as IPMN with high-risk stigmata. Abdominal computed tomography (CT) showed a 37-mm-wide cystic tumor with a contrasted solid nodule in the pancreatic head and a 17-mm-wide cystic tumor in the pancreatic tail. We performed a total pancreatectomy for these lesions. According to histopathological and immunohistochemical findings, the tumors were diagnosed as metastatic pancreatic tumors from lung cancer.

Conclusion

In this case, the cystic morphology was formed by eosinophilic secretions from tumor cells, and it was difficult to distinguish from IPMN with high-risk stigmata. We consider this case, based on the variable clinical findings, an extremely rare variant of MPTLC.
Tourniquet-induced nerve compression injuries are caused by high pressure levels and gradients – a review of the evidence to guide safe surgical, pre-hospital and blood flow restriction usage
Authors: Masri Bassam A. , Eisen Andrew , Duncan Clive P. , McEwen James A.
Published: May 2020

Tourniquets in orthopaedic surgery safely provide blood free surgical fields, but their use is not without risk. Tourniquets can result in temporary or permanent injury to underlying nerves, muscles, blood vessels and soft tissues. Advances in safety, accuracy and reliability of surgical tourniquet systems have reduced nerve-related injuries by reducing pressure levels and pressure gradients, but that may have resulted in reduced awareness of potential injury mechanisms. Short-term use of pre-hospital tourniquets is effective in preventing life-threatening blood loss, but a better understanding of the differences between tourniquets designed for pre-hospital vs surgical use will provide a framework around which to develop guidelines for admitting to hospital individuals with pre-applied tourniquets. Recent evidence supports the application of tourniquets for blood flow restriction (BFR) therapy to reduce muscular atrophy, increase muscle strength, and stimulate bone growth. BFR therapy when appropriately prescribed can augment a surgeon’s treatment plan, improving patient outcomes and reducing recovery time. Key risks, hazards, and mechanisms of injury for surgical, BFR therapy, and pre-hospital tourniquet use are identified, and a description is given of how advances in personalized tourniquet systems have reduced tourniquet-related injuries in these broader settings, increasing patient safety and how these advances are improving treatment outcomes.
Magnetic resonance susceptibility weighted in evaluation of cerebrovascular diseases
Authors: Sultan Amr Yehia Abd Elmotelb , ElShafey Khalid Ismael , Hassanien Omar Ahmed , Dawoud Rasha Mahmoud
Published: May 2020

Background

Cerebrovascular diseases are considered a very hard burden as they may lead to poor outcome, and they are considered the second most common cause of morbidity and mortality after coronary artery disease. They include wide variety of diseases that affect vascularity of brain tissue with the most common one is stroke—either ischemic or hemorrhagic. The aim of the current study was to assess the role of susceptibility weighted imaging (SWI) in imaging of different cerebrovascular diseases and what would be added by SWI to different routine magnetic resonance imaging (MRI) sequences.

Results

Fifty-five patients enrolled in this study, 14 patients had lesions with calcifications, 13 patients had cavernoma, 10 patients had diffuse axonal injury, 11 patients with infarction, 2 patients with AVM, 2 patients with chronic microbleed, 2 patients with hemorrhage, and 1 patient with hemorrhagic tumor, and the result showed that SWI has sensitivity 100%, specificity 60%, and accuracy 91.9% in regard to diagnosis of cavernoma while sensitivity 91.7%, specificity 50%, and accuracy 85.7% in regard to diagnosis of calcification and regarding diagnosis of diffuse axonal injury; SWI has 98.3% sensitivity, 100% specificity, and 98.4% accuracy; finally, in regard to diagnosis of hemorrhagic lesions, SWI has 96.1% sensitivity, 66.7% specificity, and 93.1% accuracy.

Conclusion

SWI is very sensitive in the diagnosis and detection of actual number of vascular malformation like cavernomas than conventional MRI. SWI adds significant diagnostic value to routine MRI sequences in regard to calcification that was nearly limited in its diagnosis by CT. Diagnosis of microbleeds becomes easier and accurate with SWI. Diffuse axonal injury was and still considered a clinical diagnosis, but SWI becomes the gold standard in its imaging diagnosis confirming the clinical one.
A day in the life of a psychiatrist in 2050: where will the algorithm take us?
Authors: Gillett George
Published: May 2020

Digital phenotyping (such as using live data from personal digital devices on sleep, activity and social media interactions) to monitor and interpret people's current mental state is a newly emerging development in psychiatry. This article offers an imaginary insight into its future potential for both psychiatrist and patient.
NOTCH1 signaling establishes the medullary thymic epithelial cell progenitor pool during mouse fetal development
Authors: Li Jie , Gordon Julie , Chen Edward L. Y. , Xiao Shiyun , Wu Luying , Zúñiga-Pflücker Juan Carlos , Manley Nancy R.
Published: May 2020

The cortical and medullary thymic epithelial cell (cTEC and mTEC) lineages are essential for inducing T cell lineage commitment, T cell positive selection and the establishment of self-tolerance, but the mechanisms controlling their fetal specification and differentiation are poorly understood. Here, we show that Notch signaling is required to specify and expand the mTEC lineage. Notch1 is expressed by and active in TEC progenitors. Deletion of Notch1 in TECs resulted in depletion of mTEC progenitors and dramatic reductions in mTECs during fetal stages, consistent with defects in mTEC specification and progenitor expansion. Conversely, forced Notch signaling in all TEC resulted in widespread expression of mTEC progenitor markers and profound defects in TEC differentiation. In addition, lineage-tracing analysis indicated that all mTECs have a history of receiving a Notch signal, consistent with Notch signaling occurring in mTEC progenitors. These data provide strong evidence for a requirement for Notch signaling in specification of the mTEC lineage.
Enhanced Golic+: highly effective CRISPR gene targeting and transgene HACKing in Drosophila
Authors: Chen Hui-Min , Yao Xiaohao , Ren Qingzhong , Chang Chuan-Chie , Liu Ling-Yu , Miyares Rosa Linda , Lee Tzumin
Published: May 2020

Gene targeting is an incredibly valuable technique. Sometimes, however, it can also be extremely challenging for various intrinsic reasons (e.g. low target accessibility or nature/extent of gene modification). To bypass these barriers, we designed a transgene-based system in Drosophila that increases the number of independent gene targeting events while at the same time enriching for correctly targeted progeny. Unfortunately, with particularly challenging gene targeting experiments, our original design yielded numerous false positives. Here, we deliver a much-improved technique, named Enhanced Golic+ (E-Golic+). E-Golic+ incorporates genetic modifications to tighten lethality-based selection while simultaneously boosting efficiency. With E-Golic+, we easily achieve previously unattainable gene targeting. Additionally, we built an E-Golic+-based, high-efficiency genetic pipeline for transgene swapping. We demonstrate its utility by transforming GAL4 enhancer-trap lines into tissue-specific Cas9-expressing lines. Given the superior efficiency, specificity and scalability, E-Golic+ promises to expedite development of additional sophisticated genetic/genomic tools in Drosophila.
The stem-like STAT3-responsive cells of zebrafish intestine are WNT/β-catenin dependent
Authors: Peron Margherita , Dinarello Alberto , Meneghetti Giacomo , Martorano Laura , Facchinello Nicola , Vettori Andrea , Licciardello Giorgio , Tiso Natascia , Argenton Francesco
Published: May 2020

The transcription factor STAT3 is required for proliferation and pluripotency of embryonic stem cells; we have prepared and characterized fluorescent STAT3-reporter zebrafish based on repeats of minimal responsive elements. These transgenic lines mimic in vivo STAT3 expression patterns and are responsive to exogenous STAT3; notably, fluorescence is inhibited by both stat3 knock-out and IL6/JAK/STAT inhibitors. At larval stages, STAT3 reporter activity correlates with proliferating regions of the brain, haematopoietic tissue and intestine. In the adult gut the reporter is active in sparse proliferating cells, located at the base of intestinal folds, expressing the stemness marker sox9b and having the mammalian Crypt Base Columnar cells morphology; noteworthy, zebrafish stat3 mutants show defects in intestinal folding. The STAT3 reporter activity in the gut is abolished in mutants of Tcf7l2, the intestinal mediator of Wnt/β-catenin-dependent transcription, and the Wnt/β-catenin dependence of STAT3 activity in the gut is confirmed by abrupt expansion of STAT3-positive cells in intestinal adenomas of apc heterozygotes. Our findings indicate that Jak/STAT3 signalling is needed for intestinal stem cells maintenance and possibly crucial in controlling Wnt/β-catenin-dependent colorectal cancer cells proliferation.
Neurodevelopmental disorder risk gene DYRK1A is required for ciliogenesis and brain size in Xenopus embryos
Authors: Willsey Helen Rankin , Xu Yuxiao , Everitt Amanda , Dea Jeanselle , Exner Cameron R. T. , Willsey A. Jeremy , State Matthew W. , Harland Richard M.
Published: May 2020

DYRK1A (dual specificity tyrosine-(Y)-phosphorylation-regulated kinase 1 A) is a high confidence autism risk gene that encodes a conserved kinase. In addition to autism, patients with putative loss of function variants in DYRK1A exhibit microcephaly, intellectual disability, developmental delay, and/or congenital anomalies of the kidney and urinary tract. DYRK1A is also located within the critical region for Down syndrome; therefore, understanding the role of DYRK1A in brain development is crucial for understanding the pathobiology of multiple developmental disorders. To characterize the function of this gene, we used the diploid frog, Xenopus tropicalis. We discover that Dyrk1a is expressed in ciliated tissues, localizes to ciliary axonemes and basal bodies, and is required for ciliogenesis. We also demonstrate that Dyrk1a localizes to mitotic spindles and that its inhibition leads to decreased forebrain size, abnormal cell cycle progression, and cell death during brain development. These findings provide hypotheses about potential mechanisms of pathobiology and underscore the utility of X. tropicalis as a model system for understanding neurodevelopmental disorders.
Investigating cell cycle-dependent gene expression in the context of nuclear architecture at single-allele resolution
Authors: Dhuppar Shivnarayan , Mazumder Aprotim
Published: May 2020

Nuclear architecture is the organization of the genome within a cell nucleus with respect to different nuclear landmarks such as the nuclear lamina, nuclear matrix or nucleoli. Recently, nuclear architecture has emerged as a major regulator of gene expression in mammalian cells. However, studies connecting nuclear architecture with gene expression are largely population-averaged and do not report on the heterogeneity in genome organization or gene expression within a population. In this report we present a method for combining 3D DNA fluorescence in situ hybridization (FISH) with single-molecule RNA FISH (smFISH) and immunofluorescence to study nuclear architecture-dependent gene regulation on a cell-by-cell basis. We further combine our method with imaging-based cell cycle staging to correlate nuclear architecture with gene expression across the cell cycle. We present this in the context of the cyclin-A2 (CCNA2) gene, which has known cell cycle-dependent expression. We show that, across the cell cycle, the expression of a CCNA2 gene copy is stochastic and depends neither on its sub-nuclear position – which usually lies close to nuclear lamina – nor on the expression from other copies of the gene.

This article has an associated First Person interview with the first author of the paper.
Patient Age and Survival After Surgery for Esophageal Cancer
Authors: Lagergren Jesper , Bottai Matteo , Santoni Giola
Published: May 2020

Background

Esophagectomy for esophageal cancer is associated with a substantial risk of life-threatening complications and a limited long-term survival. This study aimed to clarify the controversial questions of how age influences short-term and long-term survival.

Methods

This population-based cohort study included almost all patients who underwent curatively intended esophagectomy for esophageal cancer in Sweden in 1987–2010, with follow-up through 2016. The exposure was age, analyzed both as a continuous and categorical variable. The probability of mortality was computed using a novel flexible parametric model approach. The reported probabilities are proper measures of the risk of dying, and the related odds ratios (OR) are therefore more suitable measures of association than hazard ratios. The outcomes were 90-day all-cause mortality, 5-year all-cause mortality, and 5-year disease-specific mortality. A novel flexible parametric model was used to derive the instantaneous probability of dying and the related OR along with 95% confidence intervals (CIs), adjusted for sex, education, comorbidity, tumor histology, pathological tumor stage, and resection margin status.

Results

Among 1737 included patients, the median age was 65.6 years. When analyzed as a continuous variable, older age was associated with slightly higher odds of 90-day all-cause mortality (OR 1.05, 95% CI 1.02–1.07), 5-year all-cause mortality (OR 1.02, 95% CI 1.01–1.03), and 5-year disease-specific mortality (OR 1.01, 95% CI 1.01–1.02). Compared with patients aged < 70 years, those aged 70–74 years had no increased risk of any mortality outcome, while patients aged ≥ 75 years had higher odds of 90-day mortality (OR 2.85, 95% CI 1.68–4.84), 5-year all-cause mortality (OR 1.56, 95% CI 1.27–1.92), and 5-year disease-specific mortality (OR 1.38, 95% CI 1.09–1.76).

Conclusions

Patient age 75 years or older at esophagectomy for esophageal cancer appears to be an independent risk factor for higher short-term mortality and lower long-term survival.
Expert-Captured Democracies
Authors: Chakraborty Archishman , Ghosh Parikshit , Roy Jaideep
Published: May 2020

Does public cheap talk by a biased expert benefit voters? The answer depends on the nature of democratic institutions and the extent of communication possibilities. Expert endorsements induce office-seeking parties to serve the expert’s interests, hurting voters. Expert advocacy makes policies respond to information, helping voters. Together, policy advocacy and partisan endorsements are often better than either alone. Their interaction creates a delegation benefit that makes indirect democracy superior to direct democracy and office-seeking parties better than those motivated by public interest. But voter welfare is highest when an expert captured technocratic party competes against an uninformed populist one. (JEL D72, D82)
A comparison of manually populated radiology information system digital radiographic data with electronic dose management systems
Authors: Dickinson Nathan , Dunn Matthew
Published: May 2020

Objective:

To assess the accuracy and agreement of radiology information system (RIS) kerma–area product (KAP) data with respect to automatically populated dose management system (DMS) data for digital radiography (DR).

Methods:

All adult radiographic examinations over 12 months were exported from the RIS and DMS at three centres. Examinations were matched by unique identifier fields, and grouped by examination type. Each centre’s RIS sample completeness was calculated, as was the percentage of the RIS examination KAP values within 5% of their DMS counterparts (used as an accuracy metric). For each centre, the percentage agreement between the RIS and DMS examination median KAP values was computed using a Bland–Altman analysis. At two centres, up to 42.5% of the RIS KAP units entries were blank or invalid; corrections were attempted to improve data quality in these cases.

Results:

Statistically significant intersite variation was seen in RIS data accuracy and the agreement between the uncorrected RIS and DMS median KAP data, with a Bland–Altman bias of up to 11.1% (with a −31.7% to 53.9% 95% confidence interval) at one centre. Attempts to correct invalid KAP units increased accuracy but produced worse agreement at one centre, a slight improvement at another and no significant change in the third.

Conclusion:

The RIS data poorly represented the DMS data.

Advances in knowledge:

RIS KAP data are a poor surrogate for DMS data in DR. RIS data should only be used in patient dose surveys with an understanding of its limitations and potential inaccuracies.
Emerging strategies to target cancer metabolism and improve radiation therapy outcomes
Authors: Kery Martin , Papandreou Ioanna
Published: May 2020

Cancer-specific metabolic changes support the anabolic needs of the rapidly growing tumor, maintain a favorable redox balance, and help cells adapt to microenvironmental stresses like hypoxia and nutrient deprivation. Radiation is extensively applied in a large number of cancer treatment protocols but despite its curative potential, radiation resistance and treatment failures pose a serious problem. Metabolic control of DNA integrity and genomic stability can occur through multiple processes, encompassing cell cycle regulation, nucleotide synthesis, epigenetic regulation of gene activity, and antioxidant defenses. Given the important role of metabolic pathways in oxidative damage responses, it is necessary to assess the potential for tumor-specific radiosensitization by novel metabolism-targeted therapies. Additionally, there are opportunities to identify molecular and functional biomarkers of vulnerabilities to combination treatments, which could then inform clinical decisions. Here, we present a curated list of metabolic pathways in the context of ionizing radiation responses. Glutamine metabolism influences DNA damage responses by mechanisms such as synthesis of nucleotides for DNA repair or of glutathione for ROS detoxification. Repurposed oxygen consumption inhibitors have shown promising radiosensitizing activity against murine model tumors and are now in clinical trials. Production of 2-hydroxy glutarate by isocitrate dehydrogenase1/2 neomorphic oncogenic mutants interferes with the function of α-ketoglutarate-dependent enzymes and modulates Ataxia Telangiectasia Mutated (ATM) signaling and glutathione pools. Radiation-induced oxidative damage to membrane phospholipids promotes ferroptotic cell loss and cooperates with immunotherapies to improve tumor control. In summary, there are opportunities to enhance the efficacy of radiotherapy by exploiting cell-inherent vulnerabilities and dynamic microenvironmental components of the tumor.
BioXmark® liquid fiducial markers for image-guided radiotherapy in muscle invasive bladder cancer: a safety and performance trial
Authors: de Ridder Mischa , Gerbrandy Lara C , de Reijke Theo M , Hinnen Karel A , Hulshof Maarten C.C.M.
Published: May 2020

Objective:

This study evaluated the performance of the novel liquid fiducial marker (BioXmark®) in IGRT for bladder cancer.

Methods:

20 patients with muscle invasive bladder cancer were entered in this prospective, single center, Phase I-II study. The novel BioXmark® liquid markers were injected around the tumor using a flexible cystoscopy. Visibility and stability of the markers were evaluated on planning-CT and CBCT. Prospectively defined threshold for success was set at a visibility of 75%.

Results:

In total, 76 markers were implanted in 20 patients. Of those, 60 (79% 95% CI ± 9%) were visible on CT scan. Due to the learning curve of the technique, the visibility improved in the last 75% of patients (86% visibility) compared to the first 25% of patients with 58% visibility. Concerning stability of the BioXmark® marker, all visible markers after CT acquisition were still detectable at the last CBCT without displacement. In 15/20 (75%) of the patients, three or more markers were visible on CT. No BioXmark® related adverse events were reported.

Conclusion:

The success rate of this novel fiducial marker was 79%, which is above the prospectively defined threshold rate. A distinct learning curve of the injection of the liquid marker was seen over the study period. The marker showed sustained visibility and positional stability during treatment phases and also appears to be safe and easy to inject.

Advances in knowledge:

This novel liquid BioXmark® marker seems to be a very promising tool in daily-adaptive IGRT for bladder preserving chemoradiotherapy in muscle invasive bladder cancer.
Remembering people with dementia during the COVID-19 crisis
Authors: O'Shea Eamon
Published: May 2020

This letter argues that we need to pay particular attention to people with dementia during this difficult time of the COVID-19 pandemic. Social distancing rules and cocooning for people aged 70 years and over are now in place in Ireland to slow down the rate of infection and protect vulnerable older people.  This letter argues that we need, more than ever, to assert the personhood of people with dementia at this difficult time. That means more person-centred care and practical support structures for family carers to allow them to continue to care at home in a safe and life-enhancing way. New public broadcasting initiatives could create information and communication channels for people with dementia and their carers, as well as demonstrating empathy and solidarity with their predicament. Government, the Department of Health, the HSE and the voluntary sector have risen to the challenge of COVID-19 in all sectors of society. So too have ordinary citizens. Now we need to unite even more to create an unyielding commitment and adherence to the principles of  decency, justice  and equity in the allocation of scarce  health and social care resources. By doing this, we will demonstrate our caring potential and capacity in a way that reflects our shared humanity, not only in the current crisis, but into the future.
Bacille Calmette-Guérin Osteomyelitis of the Distal Radius in a Toddler
Authors: Kim Ji-Young , Jeon Ji-In , Chang Hak
Published: May 2020

BCG (Bacille Calmette-Guérin) vaccine has been administered safely to billions of people all over the world. The Tokyo-172 strain has reported to have a lower virulence and side effects than other strains. BCG osteomyelitis of distal radius is a very rare but serious complication due to generalized dissemination of BCG. We report a rare case of BCG osteomyelitis of the distal radius in a 21-month-old girl who had no underlying disorders. Although uncommon, BCG osteomyelitis should be considered a possible complication of BCG vaccination under certain clinical features for early diagnosis and proper treatment.
Provably Near-Optimal Approximation Schemes for Implicit Stochastic and Sample-Based Dynamic Programs
Authors: Halman Nir
Published: May 2020

In this paper, we address two models of nondeterministic discrete time finite-horizon dynamic programs (DPs): implicit stochastic DPs (the information about the random events is given by value oracles to their cumulative distribution functions) and sample-based DPs (the information about the random events is deduced by drawing random samples). Such data-driven models frequently appear in practice, where the cumulative distribution functions of the underlying random variables are either unavailable or too complicated to work with. In both models, the single-period cost functions are accessed via value oracle calls and assumed to possess either monotone or convex structure. We develop the first near-optimal relative approximation schemes for each of the two models. Applications in stochastic inventory control (that is, several variants of the so-called newsvendor problem) are discussed in detail. Our results are achieved by a combination of Bellman equation calculations, density estimation results, and extensions of the technique of K-approximation sets and functions introduced by Halman et al. (2009) [Halman N, Klabjan D, Mostagir M, Orlin J, Simchi-Levi D (2009) A fully polynomial time approximation scheme for single-item stochastic inventory control with discrete demand. Math. Oper. Res. 34(3):674–685.].
Patient safety reports round-up during the COVID-19 pandemic
Authors: Tingle John
Published: May 2020

John Tingle, Lecturer in Law, Birmingham Law School, University of Birmingham, discusses some recent patient safety reports, revealing that patient safety concerns continue during the current pandemic
From staff nurse to nurse consultant: Survival Guide part 12: Surviving social media
Authors: Fowler John
Published: May 2020

John Fowler, Educational Consultant, explores how to survive your nursing career
How you can ‘surf the wave’
Authors: Wax Ruby
Published: May 2020

Last month, Ruby Wax helped the dental world cope with the COVID-19 crisis in a successful Update Webinar
Taking the lead: management during a crisis
Authors: Price Lauren
Published: May 2020

Lauren Price is practice manager at Bath Orthodontics. Here, she shares her lockdown experience
What a difference a few years makes
Authors: Griffiths Vicki
Published: May 2020

Vicki Griffiths started the decade as a dental nurse and ended it as a dental hygienist and therapist but with ‘significantly more wrinkles ‘. Here, she shares her journey
Plant the seeds…
Authors: Middleton Anna
Published: May 2020

Former dental nurse and dental hygienist Anna Middleton considers how you nurture change in patients' understanding of tooth erosion
El afloramiento del papel de las mujeres en la cartografía y la geología : aportaciones desde la Cartoteca de Cataluña.
Authors: Ramos Espinosa Noelia
Published: May 2020

This article describes the activities designed by the Map Library of Catalonia to draw attention to the contributions of women to Earth sciences, a field traditionally dominated by men. The Library’s two main lines of action are the organization of exhibitions to bring its holdings to a wider public, and its project to develop more gender-balanced collections.
Design and analysis of a hybrid optical system containing a multilayer diffractive optical element with improved diffraction efficiency
Authors: Mao Shan , Zhao Jianlin
Published: May 2020

We present a compressive image quality evaluation for a hybrid optical system containing a multilayer diffractive optical element (MLDOE). We take effects from both incident angle and waveband into consideration to improve the diffraction efficiency of the MLDOE. With this MLDOE design, it can ensure accurate image quality evaluation for hybrid optical systems. The results show that this design enables a diffraction-efficiency-improved MLDOE, and further ensures accurate image quality of the modulation transfer function and better optical system structure of the hybrid surveillance lens. The results are of great significance for the optimal design of hybrid imaging optical systems.
Reflective temperature sensor based on a fiber Bragg grating combined with a fiber loop ringdown technique
Authors: Ning Mao Bang , Wei Chen Wen , Liu Zhao Chun , Shi Yan , Yu Shen Chang , Zhong Jin Shang
Published: May 2020

In this paper, a reflective fiber sensing system combined with a fiber loop ringdown technique for temperature detection is proposed. A fiber Bragg grating (FBG) with an initial center wavelength of 1543.33 nm was set as the sensor head. The experimental results showed that the average sensitivity of temperature was 1.003 µs/°C in the temperature range of 30–38°C, and the resolution was 0.007°C, which is 14 times better than the current FBG sensing demodulator. In addition, the system has the advantages of simple structure, low cost, and insensitivity to optical power fluctuation.
Dilp-2–mediated PI3-kinase activation coordinates reactivation of quiescent neuroblasts with growth of their glial stem cell niche
Authors: Yuan Xin , Sipe Conor W. , Suzawa Miyuki , Bland Michelle L. , Siegrist Sarah E.
Published: May 2020

Dietary nutrients provide macromolecules necessary for organism growth and development. In response to animal feeding, evolutionarily conserved growth signaling pathways are activated, leading to increased rates of cell proliferation and tissue growth. It remains unclear how different cell types within developing tissues coordinate growth in response to dietary nutrients and whether coordinated growth of different cell types is necessary for proper tissue function. Using the early Drosophila larval brain, we asked whether nutrient-dependent growth of neural stem cells (neuroblasts), glia, and trachea is coordinated and whether coordinated growth among these major brain cell types is required for neural development. It is known that in response to dietary nutrients and PI3-kinase activation, brain and ventral nerve cord neuroblasts reactivate from quiescence and ventral nerve cord glia expand their membranes. Here, we assay growth in a cell-type specific manner at short time intervals in the brain and determine that growth is coordinated among different cell types and that coordinated growth is mediated in part through activation of PI3-kinase signaling. Of the 7 Drosophila insulin-like peptides (Dilps), we find that Dilp-2 is required for PI3-kinase activation and growth coordination between neuroblasts and glia in the brain. Dilp-2 induces brain cortex glia to initiate membrane growth and make first contact with quiescent neuroblasts. Once reactivated, neuroblasts promote cortex glia growth to ultimately form a selective membrane barrier. Our results highlight the importance of bidirectional growth signaling between neural stem cells and surrounding cell types in the brain in response to nutrition and demonstrate how coordinated growth among different cell types drives tissue morphogenesis and function.