bluuebunny/crossref_metadata_2025 huggingface dataset:
A synthetic gene circuit for imaging-free detection of dynamic cell signaling
Authors: Ravindran Pavithran T. , McFann Sarah , Toettcher Jared E.
Published: January 2021

Cells employ intracellular signaling pathways to sense and respond to changes in their external environment. In recent years, live-cell biosensors have revealed complex pulsatile dynamics in many pathways, but studies of these signaling dynamics are limited by the necessity of live-cell imaging at high spatiotemporal resolution1. Here, we describe an approach to infer pulsatile signaling dynamics from just a single measurement in fixed cells using a pulse-detecting gene circuit. We computationally screened for circuit with pulse detecting capability, revealing an incoherent feedforward topology that robustly performs this computation. We then implemented the motif experimentally for the Erk signaling pathway using a single engineered transcription factor and fluorescent protein reporter. Our ‘recorder of Erk activity dynamics’ (READer) responds sensitively to both spontaneous and stimulus-driven Erk pulses. READer circuits thus open the door to permanently labeling transient, dynamic cell populations to elucidate the mechanistic underpinnings and biological consequences of signaling dynamics.
Gender differences in the Israeli academia: a bibliometric analysis of different disciplines
Authors: Cooper Tzipi , Aharony Noa , Bar-Ilan Judit
Published: January 2021

Purpose

This study explores faculty members' outputs and citations by gender and academic rank in Israeli academia. The study focuses on the connection between research productivity and underrepresentation of women in academia. To this end, four fields were chosen, each representing a different discipline: Psychology (social sciences), Public Health (health sciences), Linguistics (humanities), and Chemistry (Exact sciences).

Design/methodology/approach

The name, the rank and the gender of the researchers were collected from the researchers' websites and those of their departments. The number of publications and citations were retrieved from Scopus.

Findings

Findings revealed that there is a significant difference between the median number of men and women in Chemistry concerning publications and citations and in Psychology concerning citations. Moreover, in all four disciplines, females' average number of publications was lower than that of males', and that in three out of the four disciplines (Psychology, Public Health and Chemistry), men published more in top journals (the top 5%) than females, while the reverse was true of Linguistics. Furthermore, in three disciplines (Public Health, Linguistics and Chemistry), there is an increase in the average citations per female researchers between 2015 and 2019. Further, in all disciplines, women collaborated more than men.

Originality/value

As only a few studies in Israel have explored faculty members' outputs and citations, this study contributes and enlarges the Israeli research concerning this topic.
The cost disease blues–do the police suffer from Baumol's cost disease?
Authors: Vuorensyrjä Matti
Published: January 2021

Purpose

The purpose of this study is to analyze the growth of unit costs per output in the Finnish police force (2002–2015). Is it higher than the growth of prices in the Finnish economy in general; i.e. higher than the inflation rate? Cost disease theory suggests this to be the case. It says that all labor-intensive, slow-progressive industries suffer from relatively rapidly growing real unit costs and that policing is one among these industries.

Design/methodology/approach

The rates of growth of the division-specific unit costs of the police are compared to the inflation rate. Costs and prices are treated as indexed schedules, comparable to each other. The functional divisions under scrutiny are surveillance and emergency operations, criminal investigation, and permits and licenses. The period under analysis is 2002–2015.

Findings

The surveillance and emergency operations and criminal investigation divisions, but not the permits and licenses division, suffer from cost disease. Owing to the persistent digitalization efforts in permits and licenses, the physical productivity of the division has been growing at a rapid rate, and both the nominal and the real unit costs per output of the division have been decreasing over time.

Research limitations/implications

Owing to data limitations, use of a proxy was needed to estimate one of the key variables of the study.

Originality/value

The policy significance of the research question is potentially very high. Prior to this study, there was a near total lack of empirical evidence in this area.
Predictors of endometrial carcinoma in patients with atypical endometrial hyperplasia at a tertiary gynaecological cancer centre in Western Australia
Authors: Rajadurai Vinita Angeline , Chivers Paola , Ayres Chloe , Mohan Ganendra Raj , Stewart Colin John Reid , Leung Yee Chit , Wan King Man , Cohen Paul Andrew
Published: January 2021

Aim

Our objective was to assess clinical and pathological factors associated with a final diagnosis of endometrial carcinoma in patients with atypical endometrial hyperplasia with a particular emphasis on the grading of atypia.

Materials and methods

A retrospective review over five years on patients (N = 97) who underwent hysterectomy for a diagnosis of atypical endometrial hyperplasia at a statewide public tertiary gynaecologic oncology centre. Clinical and pathological characteristics were obtained.

Results

The rate of concurrent endometrial carcinoma was 34% (n = 33) with most being stage 1A endometrioid. A significant group difference was reported for age at diagnosis (t = −2.20 P = 0.031 d = 0.43) with carcinoma patients on average older (Mage = 60.2 (8.9) years) than patients without carcinoma (Mage = 55.5 (12.3) years). No significant group differences were found for body mass index, endometrial thickness or time between diagnosis and treatment. Significantly higher rates of carcinoma were reported in patients with moderate atypical hyperplasia (27.6%) and severe atypical hyperplasia (66.7%), compared to mild atypical hyperplasia (7.1%). Only severe atypical hyperplasia (odds ratio (OR) = 21.5, 95% CI 2.8–163.1, P = 0.003) and postmenopausal status (OR = 13.2, 95% CI 1.3–139.0, P = 0.032) significantly increased the risk of carcinoma in a multivariate model.

Conclusion

Severe atypical hyperplasia and postmenopausal status were significant predictors of concurrent endometrial carcinoma in patients with atypical endometrial hyperplasia. The grading of atypical hyperplasia may be utilised by gynaecologic oncologists in the triage and referral process of managing these patients; however, the grading system requires external validation in larger prospective studies.
Real‐world data on microsatellite instability status in various unresectable or metastatic solid tumors
Authors: Akagi Kiwamu , Oki Eiji , Taniguchi Hiroya , Nakatani Kaname , Aoki Daisuke , Kuwata Takeshi , Yoshino Takayuki
Published: January 2021

Microsatellite instability‐high (MSI‐H) is an important biomarker for predicting the effect of immune checkpoint inhibitors (ICIs) on advanced solid tumors. Microsatellite instability‐high is detected in various cancers, but its frequency varies by cancer type and stage. Therefore, precise frequency is required to plan ICI therapy. In this study, the results of MSI tests actually carried out in clinical practice were investigated. In total, 26 469 samples of various cancers were examined between December 2018 and November 2019 to determine whether programmed cell death‐1 blockade was indicated. The results of MSI tests were obtained for 26 237 (99.1%) of these samples. The male : female ratio was 51:49 and mean age was 64.3 years. In all samples, the overall frequency of MSI‐H was 3.72%. By gender, the frequency of MSI‐H was higher in female patients (4.75%) than in male patients (2.62%; P < .001). A comparison by age revealed that the frequency of MSI‐H was significantly higher in patients younger than 40 years of age (6.12%) and 80 years or older (5.77%) than in patients aged between 60 and 79 years (3.09%; P < .001). Microsatellite instability‐high was detected in 30 cancer types. Common cancer types were: endometrial cancer, 16.85%; small intestinal cancer, 8.63%; gastric cancer, 6.74%; duodenal cancer, 5.60%; and colorectal cancer, 3.78%. Microsatellite instability‐high was detected in cancer derived from a wide variety of organs. The frequency of MSI‐H varied by cancer type and onset age. These data should prove especially useful when considering ICI treatment.
Regulation of oral antigen delivery early in life: Implications for oral tolerance and food allergy
Authors: Yokanovich Lila T. , Newberry Rodney D. , Knoop Kathryn A.
Published: January 2021

The increasing incidence of food allergy remains a significant public health concern. Food allergy is partially due to a lack, or loss of tolerance to food allergens. Clinical outcomes surrounding early life practices, such as breastfeeding, antibiotic use and food allergen exposure, indicate the first year of life in children represents a unique time for shaping the immune system to reduce allergic outcomes. Animal models have identified distinctive aspects of when and where dietary antigens are delivered within the intestinal tract to promote oral tolerance prior to weaning. Additionally, animal models have identified contributions from maternal proteins from breast milk and bacterial products from the gut microbiota in regulating dietary antigen exposure and promoting oral tolerance, thus connecting decades of clinical observations on the benefits of breastfeeding, early food allergen introduction and antibiotic avoidance in the first year of life in reducing allergic outcomes. Here, we discuss how exposure to gut luminal antigens, including food allergens, is regulated in early life to generate protective tolerance and the implications of this process for preventing and treating food allergies.
Neck CT imaging and correlation with thyroid cancer incidence across age, gender and race
Authors: Ma Grace M. Y. , Makary Mina S. , Shujaat Taimur M. , Prevedello Luciano M. , Erdal Selnur B. S. , Nguyen Xuan V.
Published: January 2021

Objective

Incidental detection of thyroid cancers has been proposed as a cause of thyroid cancer increases over past decades, but few studies assess the impact of imaging utilization on thyroid cancer incidence. This study quantifies neck CT prevalence and its relationship with thyroid cancer incidence as a function of age, sex and race.

Design and Patients

Medical records of over 1 million patients at our institution were retrospectively analysed to quantify neck CT prevalence from 2004 to 2011 (study period). A national cancer database was used to compute thyroid cancer incidences over the study period and a reference period (1974‐81) and to calculate change in thyroid incidence between the two periods. Both populations were partitioned into demographic subgroups of varying age, sex and race. Linear correlation between neck imaging and thyroid cancer incidence changes among subgroups was assessed using Pearson's correlation.

Results

Neck CT imaging and change in thyroid cancer incidence varied across all examined demographic variables, particularly age. When stratifying by age, CT use correlated strongly with recent national thyroid cancer incidence (R = .97) and with 30‐year change in thyroid cancer incidence (R = .87). Across all demographic subgroups, CT prevalence correlated strongly and positively with change in thyroid cancer incidence (R = .60), greater for whites (R = .60) and blacks (R = .70) than other races (R = .28).

Conclusion

Differences in neck CT usage strongly and positively correlates with the variation in thyroid cancer trends based on age, gender and race.
Automatic Image Checkpoint Selection for Guider‐Follower Pedestrian Navigation
Authors: Kwan K. C. , Fu H.
Published: January 2021

In recent years guider‐follower approaches show a promising solution to the challenging problem of last‐mile or indoor pedestrian navigation without micro‐maps or indoor floor plans for path planning. However, the success of such guider‐follower approaches is highly dependent on a set of manually and carefully chosen image or video checkpoints. This selection process is tedious and error‐prone. To address this issue, we first conduct a pilot study to understand how users as guiders select critical checkpoints from a video recorded while walking along a route, leading to a set of criteria for automatic checkpoint selection. By using these criteria, including visibility, stairs and clearness, we then implement this automation process. The key behind our technique is a lightweight, effective algorithm using left‐hand‐side and right‐hand‐side objects for path occlusion detection, which benefits both automatic checkpoint selection and occlusion‐aware path annotation on selected image checkpoints. Our experimental results show that our automatic checkpoint selection method works well in different navigation scenarios. The quality of automatically selected checkpoints is comparable to that of manually selected ones and higher than that of checkpoints by alternative automatic methods.
Pre‐implant global longitudinal strain as an early sign of pacing‐induced cardiomyopathy in patients with complete atrioventricular block
Authors: Chin Jung Yeon , Kang Ki‐Woon , Park Sang Hyun , Choi Yu Jeong , Jung Kyung Tae , Lee Soyoung , Youn Ho‐Joong
Published: January 2021

Introduction

Long‐term right ventricular pacing is the only treatment for patients with a complete atrioventricular block (CAVB); however, it frequently triggers ventricular dys‐synchrony with left ventricular (LV) dysfunction. Previous studies showed that an early decline of LV global longitudinal strain (GLS) predicts pacing‐induced LV dysfunction. We aimed to investigate the potential ability of the initial LV strain to predict pacing‐induced cardiomyopathy (PICM) through long‐term follow‐ups.

Methods

We retrospectively enrolled 80 patients with CAVB with normal LV function who were implanted with dual‐chamber pacemakers between 2008 and 2018. Echocardiographic data and parameters (including longitudinal, radial, and circumferential strain based on speckle‐tracking) were analyzed for the pre‐implant (≤6 months) and post‐implant periods. PICM was defined as a ≥10% reduction in the left ventricular ejection fraction (LVEF) resulting in an LVEF of <50% during the post‐implant period. Predictors of PICM were identified using Cox proportional hazard models.

Results

Patients who developed PICM were more likely to exhibit lower baseline LV GLS, as well as wider native and pacing QRS durations, than those who did not develop PICM (P = .016, P = .011, and P = .026, respectively). In the multivariate analysis, pre‐implant LV GLS (hazard ratio: 1.27; 95% confidence interval 1.009–1.492; P = .004) was independently associated with the development of PICM.

Conclusion

A lower baseline LV GLS predicts an increased risk of PICM. Patients with CAVB exhibiting low GLS are at increased risk of PICM. More frequent follow‐up visits are warranted in these patients, who may also require de novo His‐bundle pacing or an upgrade to biventricular pacing.
Multifunctional intracellular matrix metalloproteinases: implications in disease
Authors: Bassiouni Wesam , Ali Mohammad A. M. , Schulz Richard
Published: January 2021

Matrix metalloproteinases (MMPs) are zinc‐dependent endopeptidases that were first discovered as proteases, which target and cleave extracellular proteins. During the past 20 years, however, intracellular roles of MMPs were uncovered and research on this new aspect of their biology expanded. MMP‐2 is the first of this protease family to be reported to play a crucial intracellular role where it cleaves several sarcomeric proteins inside cardiac myocytes during oxidative stress‐induced injury. Beyond MMP‐2, currently at least eleven other MMPs are known to function intracellularly including MMP‐1, MMP‐3, MMP‐7, MMP‐8, MMP‐9, MMP‐10, MMP‐11, MMP‐12, MMP‐14, MMP‐23 and MMP‐26. These intracellular MMPs are localized to different compartments inside the cell including the cytosol, sarcomere, mitochondria, and the nucleus. Intracellular MMPs contribute to the pathogenesis of various diseases. Cardiovascular renal disorders, inflammation, and malignancy are some examples. They also exert antiviral and bactericidal effects. Interestingly, MMPs can act intracellularly through both protease‐dependent and protease‐independent mechanisms. In this review, we will highlight the intracellular mechanisms of MMPs activation, their numerous subcellular locales, substrates, and roles in different pathological conditions. We will also discuss the future direction of MMP research and the necessity to exploit the knowledge of their intracellular targets and actions for the design of targeted inhibitors.
External auditors' reliance on management's experts: The effects of an early‐stage conversation and past auditor–client relationship
Authors: Agrawal Prerana , Wang Isabel Z. , Woodliff David
Published: January 2021

This study examines the impact of an early‐stage conversation with a management's expert on auditors' decisions within the context of auditor–client relationships. We conducted a 2 × 2 between‐subjects experiment with 69 experienced auditors in Australia. Our results suggest that an early‐stage conversation can adversely affect perceived client flexibility towards proposed audit adjustments, particularly under contentious client conditions. Our results further indicate that an early‐stage conversation results in auditors relaxing, which otherwise might be a more contentious approach towards difficult clients. While we do not find direct evidence that auditors succumb to pressure and accept the work of the management's expert without any changes, our results suggest that auditors are willing to propose an adjustment that meets the interests of both auditor and client.
Bureaucrats or Ideologues? EU Merger Control as Market‐centred Integration*
Authors: Billows Sebastian , Kohl Sebastian , Tarissan Fabien
Published: January 2021

Since 1989, no major European merger has been able to go through without EU approval. The introduction of a centralized merger control procedure was another increase in the powers of the Commission's Directorate‐General for Competition (DG COMP). While some see it playing a neo‐mercantilist role in a positive European integration, others underline its neoliberal ideological roots. Through our analysis of all merger decisions made between 1990 and 2016 (6,161 cases), we instead find evidence for market‐centred negative integration: DG COMP is particularly harsh towards coordinated market economies and targets sectors that have high levels of state intervention, thus thwarting the rise of ‘European champions’. Our interviews with merger experts and the decision citation data further suggest that this market‐centred logic of enforcement is not necessarily driven by ideology, but by the silent logic of bureaucratic autonomy. We thus contribute to the debate on the EU as a supranational force of economic liberalization.
DNA methylation and histone acetylation are involved in Wnt10b expression during the secondary hair follicle cycle in Angora rabbits
Authors: Bai Liya , Sun Haitao , Jiang Wenxue , Yang Liping , Liu Gongyan , Zhao Xueyan , Hu Hongmei , Wang Jianying , Gao Shuxia
Published: January 2021

Secondary hair follicles (SHFs) in the Angora rabbit exhibit classic cyclic hair development, but the multiple molecular signals involved in hair cycling are yet to be explored in detail. In the present study, we investigated the expression pattern, methylation and histone H3 acetylation status of Wnt10b, as a molecular signal participating in hair cycling, during the SHF cycle in the Angora rabbit. Expression of Wnt10b at the anagen phase was significantly higher than that at both the telogen and catagen phases, suggesting that Wnt10b might serve as a critical activator during cyclic transition of SHFs. Methylation frequency of the fifth CpG site (CpG5‐175 bp) in CpG islands at the anagen phase was lower than that at both the catagen and telogen phases. The methylation status of the CpG5 site was negatively correlated with Wnt10b expression. This indicated that the methylation of CpG5 might participate in Wnt10b transcriptional suppression in SHFs. Furthermore, histone H3 acetylation status in the regions‐256~−11 bp and 98 ~ 361 bp were significantly lower at both the catagen and telogen phases than at the anagen phase. The histone H3 acetylation level was significantly positively correlated with Wnt10b expression. This confirmed that histone acetylation was likely involved in upregulating Wnt10b transcription in SHFs. Additionally, potential binding to the transcription factors ZF57 and HDBP was predicted within the CpG5 site. In conclusion, our findings reveal the epigenetic mechanism of Wnt10b transcription and provide a new insight into epigenetic regulation during the SHF cycle in the Angora rabbit.
Home consumption of two fortified balanced energy protein supplements by pregnant women in Burkina Faso
Authors: de Kok Brenda , Moore Katie , Jones Leslie , Vanslambrouck Katrien , Toe Laeticia Celine , Ouédraogo Moctar , Ganaba Rasmané , de Pee Saskia , Bedford Juliet , Lachat Carl , Kolsteren Patrick , Isanaka Sheila
Published: January 2021

Balanced energy protein (BEP) supplementation for pregnant and lactating women in low‐ and middle‐income countries is a promising strategy to improve birth outcomes and child growth. The objective of this study was to assess and compare the acceptability of new formulations of two fortified BEP supplements, a lipid‐based peanut paste and a vanilla biscuit, among 80 pregnant women in rural Burkina Faso, prior to an efficacy trial. A 10‐week individually randomized cross‐over study was designed, in which women received a weekly supply of each supplement for 4 weeks, and a daily choice between the supplements in the last 2 weeks. Questionnaires to assess daily consumption and supplement acceptability (n= 80) and home observations (n= 20) were combined with focus group discussions (n= 6) and in‐depth interviews with women (n= 80) and stakeholders (n= 24). Results showed that the two supplements were well accepted. Quantitative findings indicated high compliance (>99.6%) and high overall appreciation (Likert score >6 out of 7) of both supplements. The assessment of preferred choice in Weeks 9 and 10 indicated a slight preference for the vanilla biscuit. Qualitative findings indicated that perceived health benefits, support from household members and educational messages from health professionals were important drivers for acceptance and compliance. Sharing was not often reported but was identified during interviews as a possible risk. We recommend that future studies use a combination of methods to identify appropriate food supplements and context‐specific factors that influence acceptability, compliance and subsequent impact of nutritious food supplements.
Spatial pricing and collusion
Authors: Heywood John S. , Li Dongyang , Ye Guangliang
Published: January 2021

The stability of collusion is compared assuming quadratic transport costs under two spatial pricing schemes, uniform mill pricing and spatial price discrimination. This comparison uniquely allows fully endogenous location choice and examines when two firms collude, when two of three firms collude and when three firms collude. Spatial price discrimination facilitates collusion more than uniform pricing in the first two of the three examinations but not in the third. This heterogeneity argues that the presence of price discrimination by itself does not inform antitrust authorities about the likelihood of collusion.
Understanding the evolution of endosymbiotic organelles based on the targeting sequences of organellar proteins
Authors: Lee Dong Wook , Hwang Inhwan
Published: January 2021

Organellogenesis, a key aspect of eukaryotic cell evolution, critically depends on the successful establishment of organellar protein import mechanisms. Phylogenetic analysis revealed that the evolution of the two endosymbiotic organelles, the mitochondrion and the chloroplast, is thought to have occurred at time periods far from each other. Despite this, chloroplasts and mitochondria have highly similar protein import mechanisms. This raises intriguing questions such as what underlies such similarity in the import mechanisms and how these similar mechanisms have evolved. In this review, we summarise the recent findings regarding sorting and specific targeting of these organellar proteins. Based on these findings, we propose possible evolutionary scenarios regarding how the signal sequences of chloroplasts and mitochondrial proteins ended up having such relationship.
A performance‐based measure of emotion response control: A preliminary MRI study
Authors: Steinert Steven W. , Daugherty Ana M. , Shankar Sneha , Schwarb Hillary , Cerjanic Alex , Sutton Bradley P. , Arble Eamonn P.
Published: January 2021

Identifying performance‐based assessments of emotion regulation is needed for the study of myriad mood and neurological disorders. Color and form responses on the Rorschach Inkblot Method are valid measures of emotion response control, but have not been studied in relation to known neural correlations of emotion regulation. A discrepancy of color (CF + C) greater than form (FC) responses suggests low cognitive control over emotional responses. This preliminary report explores the discrepancy between form‐color responses as a correlate of regional cortical thickness. A sample of community‐dwelling adults were administered the Rorschach Inkblot Method and participated in a structural MRI scan. Greater middle frontal cortex thickness was associated with a positive discrepancy score [(CF + C) – FC], indicating less emotion response control (rs = 0.48, p < 0.05); a moderate, non‐significant correlation was also observed with insula cortex (rs = 0.42, p = 0.07).The results provide evidence in support of the Rorschach Inkblot Method as a valid behavioral measure of emotion response control. More specifically, these results support the use of color‐related variables included in contemporary evidence‐based Rorschach methods. The results are discussed with implications for the study of emotion regulation in mood disorders and sensitivity analyses based on the observed effect sizes are reported to inform future study planning.
How Do Sport Parents Engage in Autonomy-Supportive Parenting in the Family Home Setting? A Theoretically Informed Qualitative Analysis
Authors: Holt Nicholas L. , Jørgensen Helene , Deal Colin J.
Published: January 2021

The purpose of this study was to identify and examine how sport parents engage in autonomy-supportive parenting in the family home setting. A total of 44 parents and children from 19 families were initially interviewed. Data from these families were profiled to identify seven families that adopted a highly autonomy-supportive parenting style. The seven families’ data were then examined using a theoretically focused qualitative analysis using the three dimensions of autonomy-supportive parenting. Sport parents engaged in autonomy support (vs. control) through flexible conversations and supporting decision making. The themes of boundary setting and establishing expectations based on values were indicative of structure. The authors found high levels of involvement across contexts. These findings depict the nature and types of social interactions in the family home that created an autonomy-supportive emotional climate, which often extended to sport, providing a foundation for future theoretical development and applied research in sport.
Brexit deal secures U.K. access to research funds
Authors: Wallace Nicholas
Published: January 2021

Horizon Europe program will be open to U.K. researchers.
Alternatives to black holes are scarce and strange
Authors: Cho Adrian
Published: January 2021

General relativity doesn't leave lots of wiggle room for new ideas, theorists say.
Insight into Vaccine Development for Alphacoronaviruses Based on Structural and Immunological Analyses of Spike Proteins
Authors: Shi Yuejun , Shi Jiale , Sun Limeng , Tan Yubei , Wang Gang , Guo Fenglin , Hu Guangli , Fu Yanan , Fu Zhen F. , Xiao Shaobo , Peng Guiqing
Published: January 2021

Outbreaks of coronaviruses, especially SARS-CoV-2, pose a serious threat to global public health. Development of vaccines to prevent the coronaviruses that can infect humans has always been a top priority.
Acute oesophageal necrosis in multiple endocrine neoplasia type 1: an undescribed complication
Authors: Bhattacharya Sumona , Blau Jenny E , Koh Christopher
Published: January 2021

Acute oesophageal necrosis (AEN) is a rare entity that most commonly presents as upper gastrointestinal bleeding. Complex pathophysiology may include oesophageal ischaemia as well as reflux of acidic gastric contents causing oesophageal mucosal injury. Management is supportive and directed at underlying comorbidities however prognosis is poor with complications such as oesophageal perforation, stricture and stenosis. Here we present the case of a 56-year-old man with multiple endocrine neoplasia type 1 (MEN1) and gastro-oesophageal reflux disease who developed AEN as a result of undiagnosed Zollinger-Ellison syndrome (ZES), duodenal ulcer-induced obstruction and hypotension from new-onset atrial fibrillation. AEN as the presentation of MEN1-associated ZES is an unusual presentation of this disease which clinicians, particularly endocrinologists and endoscopists, should be aware of.
No evidence that vitamin D is able to prevent or affect the severity of COVID-19 in individuals with European ancestry: a Mendelian randomisation study of open data
Authors: Amin Hasnat A , Drenos Fotios
Published: January 2021

Background

Upper respiratory tract infections are reportedly more frequent and more severe in individuals with lower vitamin D levels. Based on these findings, it has been suggested that vitamin D can prevent or reduce the severity of COVID-19.

Methods

We used two-sample Mendelian randomisation (MR) to assess the causal effect of vitamin D levels on SARS-CoV-2 infection risk and COVID-19 severity using publicly available data. We also carried out a genome-wide association analysis (GWA) of vitamin D deficiency in the UK Biobank (UKB) and used these results and two-sample MR to assess the causal effect of vitamin D deficiency on SARS-CoV-2 infection risk and COVID-19 severity.

Results

We found no evidence that vitamin D levels causally affect the risk of SARS-CoV-2 infection (ln(OR)=0.17 (95% CI −0.22 to 0.57, p=0.39)) nor did we find evidence that vitamin D levels causally affect COVID-19 severity (ln(OR)=0.36 (95% CI −0.89 to 1.61, p=0.57)). Based on our GWA analysis, we found that 17 independent variants are associated with vitamin D deficiency in the UKB. Using these variants as instruments for our two-sample MR analyses, we found no evidence that vitamin D deficiency causally affects the risk of SARS-CoV-2 infection (ln(OR)=−0.04 (95% CI −0.1 to 0.03, p=0.25)) nor did we find evidence that vitamin D deficiency causally affects COVID-19 severity (ln(OR)=−0.24 (95% CI −0.55 to 0.08, p=0.14)).

Conclusions

In conclusion, we found no evidence that vitamin D is protective against SARS-CoV-2 infection or COVID-19 severity. Our data support the recent statement by the National Institute for Health and Care Excellence that the use of vitamin D supplementation to mitigate COVID-19 is not supported by the available data.
Does variety of social interactions associate with frequency of laughter among older people? The JAGES cross-sectional study
Authors: Nagai Masato , Ohira Tetsuya , Shirai Kokoro , Kondo Katsunori
Published: January 2021

Objective

Several studies have reported that laughter is associated with health benefits. In addition, social interactions, such as social relationships, social participation and so forth, have shown the association with not only health but also individual emotion. In this study, we conducted a cross-sectional study to examine the association between variety of social interactions and the frequency of laughter.

Design

Cross-sectional study.

Setting

Sampled from 30 municipalities in Japan.

Participants

Non-disabled Japanese men (n=11 439) and women (n=13 159) aged ≥65 years using data from the Japan Gerontological Evaluation Study, which was conducted during October to December in 2013.

Primary outcome measures

Laughing almost every day by self-reported questionnaire.

Results

Poisson regression analysis with robust error variance was used to calculate prevalence ratios (PRs) for laughing almost every day according to each social relationship and its potential community-level environmental determinants. The prevalence of laughing almost every day tended to increase with increased variety in each social interaction after adjusting, instrumental activities of daily living, number of living together, working status, depression, self-reported economic status and residence year. Among men and women, multivariate-adjusted PRs (95% CIs) by comparing participants with the highest and lowest categories were 1.18 (1.04 to 1.35) and 1.16 (1.04 to 1.29) in positive life events; 1.26 (1.10 to 1.45) and 1.09 (0.96 to 1.24) in perceived positive changes in the area; 1.15 (1.04 to 1.28) and 1.17 (1.07 to 1.28) in social participations; 2.23 (1.57 to 3.16) and 1.47 (1.02 to 2.12) in social relationships and 1.25 (1.08 to 1.45) and 1.29 (1.15 to 1.45) in positive built environments. These associations were also preserved after the restriction of participants who were not in depression.

Conclusions

This study shows that a greater variety of each social relationships and the potential community-level environmental determinants are associated with higher frequencies of laughter in Japan.
Prevalence of retinopathy in prediabetes: protocol for a systematic review and meta-analysis
Authors: Kirthi Varo , Nderitu Paul , Alam Uazman , Evans Jennifer , Nevitt Sarah , Malik Rayaz A , Jackson Timothy L
Published: January 2021

Introduction

There is growing evidence of a higher than expected prevalence of retinopathy in prediabetes. This paper presents the protocol of a systematic review and meta-analysis of retinopathy in prediabetes. The aim of the review is to estimate the prevalence of retinopathy in prediabetes and to summarise the current data.

Methods and analysis

This protocol is developed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) guidelines. A comprehensive electronic bibliographic search will be conducted in MEDLINE, EMBASE, Web of Science, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Google Scholar and the Cochrane Library. Eligible studies will report prevalence data for retinopathy on fundus photography in adults with prediabetes. No time restrictions will be placed on the date of publication. Screening for eligible studies and data extraction will be conducted by two reviewers independently, using predefined inclusion criteria and prepiloted data extraction forms. Disagreements between the reviewers will be resolved by discussion, and if required, a third (senior) reviewer will arbitrate.

The primary outcome is the prevalence of any standard features of diabetic retinopathy (DR) on fundus photography, as per International Clinical Diabetic Retinopathy Severity Scale (ICDRSS) classification. Secondary outcomes are the prevalence of (1) any retinal microvascular abnormalities on fundus photography that are not standard features of DR as per ICDRSS classification and (2) any macular microvascular abnormalities on fundus photography, including but not limited to the presence of macular exudates, microaneurysms and haemorrhages. Risk of bias for included studies will be assessed using a validated risk of bias tool for prevalence studies. Pooled estimates for the prespecified outcomes of interest will be calculated using random effects meta-analytic techniques. Heterogeneity will be assessed using the I2statistic.

Ethics and dissemination

Ethical approval is not required as this is a protocol for a systematic review and no primary data are to be collected. Findings will be disseminated through peer-reviewed publications and presentations at national and international meetings including Diabetes UK, European Association for the Study of Diabetes, American Diabetes Association and International Diabetes Federation conferences.

PROSPERO registration number

CRD42020184820.
Using a report card to increase HIV screening in a large primary care group practice
Authors: Luu Mitchell N , Wada Paul Y , Levine-Hall Tory , Hurley Leo , Ramalingam Nirmala , Tran H Nicole , Slome Sally B
Published: January 2021

Background

Despite increased efforts to promote HIV screening, a large proportion of the US population have never been tested for HIV.

Objective

To determine whether provider education and personalised HIV screening report cards can increase HIV screening rates within a large integrated healthcare system.

Design

This quality improvement study provided a cohort of primary care physicians (PCPs) a brief educational intervention and personalised HIV screening report cards with quarterly performance data.

Participants

Participants included a volunteer cohort of 20 PCPs in the department of adult and family medicine.

Main measures

Per cent of empaneled patients screened for HIV by cohort PCPs compared with PCPs at the Kaiser Permanente Oakland Medical Center (KPOAK) and the non-Oakland Medical Centers in Northern California region (Kaiser Permanente Northern California (KPNC)).

Key results

Of the 20 participating PCPs, 13 were female and 7 were male. Thirteen were internal medicine and seven family medicine physicians. The average age was 40 years and average practice experience was 9 years after residency. During the 12-month intervention, the estimated increase in HIV screening in the cohort PCP group was 2.6% as compared with 1.9% for KPOAK and 1.8% for KPNC.

Conclusions

These findings suggest that performance-related report cards are associated with modestly increased rates of HIV screening by PCPs.
Differences in TCR repertoire and T cell activation underlie the divergent outcomes of antitumor immune responses in tumor-eradicating versus tumor-progressing hosts
Authors: Woolaver Rachel A , Wang Xiaoguang , Krinsky Alexandra L , Waschke Brittany C , Chen Samantha M Y , Popolizio Vince , Nicklawsky Andrew G , Gao Dexiang , Chen Zhangguo , Jimeno Antonio , Wang Xiao-Jing , Wang Jing Hong
Published: January 2021

Background

Antitumor immunity is highly heterogeneous between individuals; however, underlying mechanisms remain elusive, despite their potential to improve personalized cancer immunotherapy. Head and neck squamous cell carcinomas (HNSCCs) vary significantly in immune infiltration and therapeutic responses between patients, demanding a mouse model with appropriate heterogeneity to investigate mechanistic differences.

Methods

We developed a unique HNSCC mouse model to investigate underlying mechanisms of heterogeneous antitumor immunity. This model system may provide a better control for tumor-intrinsic and host-genetic variables, thereby uncovering the contribution of the adaptive immunity to tumor eradication. We employed single-cell T-cell receptor (TCR) sequencing coupled with single-cell RNA sequencing to identify the difference in TCR repertoire of CD8 tumor-infiltrating lymphocytes (TILs) and the unique activation states linked with different TCR clonotypes.

Results

We discovered that genetically identical wild-type recipient mice responded heterogeneously to the same squamous cell carcinoma tumors orthotopically transplanted into the buccal mucosa. While tumors initially grew in 100% of recipients and most developed aggressive tumors, ~25% of recipients reproducibly eradicated tumors without intervention. Heterogeneous antitumor responses were dependent on CD8 T cells. Consistently, CD8 TILs in regressing tumors were significantly increased and more activated. Single-cell TCR-sequencing revealed that CD8 TILs from both growing and regressing tumors displayed evidence of clonal expansion compared with splenic controls. However, top TCR clonotypes and TCR specificity groups appear to be mutually exclusive between regressing and growing TILs. Furthermore, many TCRα/TCRβ sequences only occur in one recipient. By coupling single-cell transcriptomic analysis with unique TCR clonotypes, we found that top TCR clonotypes clustered in distinct activation states in regressing versus growing TILs. Intriguingly, the few TCR clonotypes shared between regressors and progressors differed greatly in their activation states, suggesting a more dominant influence from tumor microenvironment than TCR itself on T cell activation status.

Conclusions

We reveal that intrinsic differences in the TCR repertoire of TILs and their different transcriptional trajectories may underlie the heterogeneous antitumor immune responses in different hosts. We suggest that antitumor immune responses are highly individualized and different hosts employ different TCR specificities against the same tumors, which may have important implications for developing personalized cancer immunotherapy.
Neuroimaging and advanced research techniques may lead to improved outcomes in military members suffering from traumatic brain injury
Authors: Moyron Ron B , Vallejos Paul A , Fuller Ryan N , Dean Natasha , Wall Nathan R
Published: January 2021

Recent military conflicts in Iraq and Afghanistan have resulted in the significant increase in blast-related traumatic brain injury (TBI), leading to increased Department of Defense interest in its potential long-term effects ranging from the mildest head injuries termed subconcussive trauma to the most debilitating termed chronic traumatic encephalopathy (CTE). Most patients with mild TBI will recover quickly while others report persistent symptoms called postconcussive syndrome. Repeated concussive and subconcussive head injuries result in neurodegenerative conditions that may hinder the injured for years. Fundamental questions about the nature of these injuries and recovery remain unanswered. Clinically, patients with CTE present with either affective changes or cognitive impairment. Genetically, there have been no clear risk factors identified. The discovery that microglia of the cerebral cortex discharged small extracellular vesicles in the injured and adjacent regions to a TBI may soon shed light on the immediate impact injury mechanisms. The combination of neuroimaging and advanced research techniques may, one day, fill critical knowledge gaps and lead to significant TBI research and treatment advancements.
Best of both worlds: hybrids of two commercially important pines (Pinus contorta × Pinus banksiana) combine increased growth potential and high drought tolerance
Authors: Bockstette Simon W. , de la Mata Raul , Thomas Barb R.
Published: January 2021

Over 18 million hectares of lodgepole pine (Pinus contorta Dougl. var. latifolia Engelm.) forests have been affected by a massive mountain pine beetle outbreak in western Canada. The ensuing need for reforestation compels forest managers to deploy more drought-resistant stock in anticipation of a hotter and drier future climate. Recent studies suggest that naturally occurring lodgepole pine × jack pine (Pinus banksiana Lamb.) hybrids may be more drought-resistant than pure lodgepole pine. We used single-nucleotide polymorphism markers to determine the level of jack pine introgression present in the region J lodgepole pine seed orchard, in northwest Alberta, and we identified six hybrid genotypes with 10%–18% jack pine introgression for further study. We compared the performance of open-pollinated seedlings of lodgepole, jack, and hybrid pines under well-watered and drought conditions in a greenhouse experiment. Seedlings were subjected to repeg ated drought cycles, withholding water for either 2 or 3 weeks. We found that hybrid pines grew significantly faster than lodgepole pine under well-watered conditions while retaining the high tolerance to prolonged drought exhibited by lodgepole pine seedlings, a particularly beneficial combination of traits during the critical stage of establishment. We therefore suggest the deployment of hybrid lodgepole pine as a strategy to promote adaptation to hotter and drier future climates.
Systematic of alpha decay half-lives: role of quantization condition
Authors: Hosseini-Tabatabaei M. , Alavi S.A. , Dehghani V.
Published: January 2021

Using the semiclassical WKB method and considering the WKB quantization condition, the alpha decay half-lives of 420 alpha emitters were calculated with eight forms of the proximity and Woods–Saxon type potentials. The effect of quantization condition on the nuclear potential, effective potential, assault frequency, tunneling probability, alpha decay half-life, and root mean square deviation between theory and the experiment were investigated. Significant differences between calculated half-lives with and without inclusion of the quantization condition were observed specially for proximity potentials. By including the quantization, the Woods–Saxon potential was found as the best potential for even–even, even–odd, odd–even, odd–odd, and all alpha emitters. The quantization condition normalized the nuclear potentials. Therefore, by considering this condition, the thirteen forms of the prox77 potential with different sets of the surface energy and surface asymmetry constants gave the same results. This result was justified with two sets of parameters.
Point defects in tight binding models for insulators
Authors: Ortner Christoph , Thomas Jack
Published: January 2021

We consider atomistic geometry relaxation in the context of linear tight binding models for point defects. A limiting model as Fermi-temperature is sent to zero is formulated, and an exponential rate of convergence for the nuclei configuration is established. We also formulate the thermodynamic limit model at zero Fermi-temperature, extending the results of [H. Chen, J. Lu and C. Ortner, Thermodynamic limit of crystal defects with finite temperature tight binding, Arch. Ration. Mech. Anal. 230 (2018) 701–733]. We discuss the non-trivial relationship between taking zero temperature and thermodynamic limits in the finite Fermi-temperature models.
Correlated Log-Normal Random Variables under a Multiscale Volatility Model
Authors: Ma Yong-Ki
Published: January 2021

The study focuses on extending the fast mean-reversion volatility, which was developed by the author in a previous work, to the multiscale volatility model so that it can express a well-separated time scale. The leading-order term and first-order correction terms are analytically computed using the perturbation theory based on the Lie–Trotter operator splitting method. Finally, the study is concluded by deriving the numerical results that further validate the effectiveness of the model.