bluuebunny/crossref_metadata_2025 huggingface dataset:
Emergence of Walnut Husk Maggot Adults in Central Illinois and Potential for Control with Metarhizium brunneum
Authors: Behle Robert W
Published: November 2020

The walnut husk maggot, Rhagoletis sauvis (Loew) (Diptera: Tephritidae), causes damage to walnuts when maggots feed inside the husk. September applications of the entomopathogenic fungi Metarhizium brunneum F52 as microsclerotia laced granules to the soil in Illinois were evaluated for pest control based on adult emergence during the following summer. Over 3 yr in central Illinois, adult emergence began near 1 July, peaked before 23 July, and emergence extended as late as 23 August. One summer application of fungus (30 June) when pupae were present, did not reduce fly emergence. Of two September applications that targeted maggots as they move to the soil to pupate, one significantly reduced the number of flies emerging from treated plots when compared with untreated plots for one 7-d sample collected 29 July 2020. Emergence trap data show a defined peak adult emergence in July for central Illinois while September applications of granules containing Metarhizium brunneum (Petch) (Hypocreales: Clavicipitaceae) show shows potential to reduced subsequent fly emergence.
Comparing 5-Year and Lifetime Risks of Breast Cancer using the Prospective Family Study Cohort
Authors: MacInnis Robert J , Knight Julia A , Chung Wendy K , Milne Roger L , Whittemore Alice S , Buchsbaum Richard , Liao Yuyan , Zeinomar Nur , Dite Gillian S , Southey Melissa C , Goldgar David , Giles Graham G , Kurian Allison W ,   kConFab Investigators, Andrulis Irene L , John Esther M , Daly Mary B , Buys Saundra S , Phillips Kelly-Anne , Hopper John L , Terry Mary Beth
Published: November 2020

Background

Clinical guidelines often use predicted lifetime risk from birth to define criteria for making decisions regarding breast cancer screening rather than thresholds based on absolute 5-year risk from current age.

Methods

We used the Prospective Family Cohort Study of 14 657 women without breast cancer at baseline in which, during a median follow-up of 10 years, 482 women were diagnosed with invasive breast cancer. We examined the performances of the International Breast Cancer Intervention Study (IBIS) and Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA) risk models when using the alternative thresholds by comparing predictions based on 5-year risk with those based on lifetime risk from birth and remaining lifetime risk. All statistical tests were 2-sided.

Results

Using IBIS, the areas under the receiver-operating characteristic curves were 0.66 (95% confidence interval = 0.63 to 0.68) and 0.56 (95% confidence interval = 0.54 to 0.59) for 5-year and lifetime risks, respectively (Pdiff < .001). For equivalent sensitivities, the 5-year incidence almost always had higher specificities than lifetime risk from birth. For women aged 20-39 years, 5-year risk performed better than lifetime risk from birth. For women aged 40 years or older, receiver-operating characteristic curves were similar for 5-year and lifetime IBIS risk from birth. Classifications based on remaining lifetime risk were inferior to 5-year risk estimates. Results were similar using BOADICEA.

Conclusions

Our analysis shows that risk stratification using clinical models will likely be more accurate when based on predicted 5-year risk compared with risks based on predicted lifetime and remaining lifetime, particularly for women aged 20-39 years.
Evaluation of the Core Formation Process in Congenital Neuromuscular Disease With Uniform Type 1 Fiber and Central Core Disease
Authors: Ogasawara Masashi , Ogawa Megumu , Nonaka Ikuya , Hayashi Shinichiro , Noguchi Satoru , Nishino Ichizo
Published: November 2020

Typical central core disease (CCD) is characterized pathologically by the presence of a core and is accompanied by type 1 fiber uniformity. Congenital neuromuscular disease with uniform type 1 fiber (CNMDU1) is characterized pathologically by the presence of type 1 fiber uniformity but without the abnormal structural changes in muscle fibers. Interestingly, typical CCD and 40% of CNMDU1 cases are caused by the same mutations in RYR1, and thus CNMDU1 has been considered an early precursor to CCD. To better understand the nature of CNMDU1, we re-evaluated muscle biopsies from 16 patients with CNMDU1 using immunohistochemistry to RYR1, triadin and TOM20, and compared this to muscle biopsies from 36 typical CCD patients. In CCD, RYR1, and triadin were present in the core regions, while TOM20 was absent in the core regions. Interestingly, in 5 CNMDU1 cases with the RYR1 mutation, RYR1, and triadin were similarly present in core-like areas, while TOM20 was absent in the subsarcolemmal region. Furthermore, there was a correlation between the core position and the disease duration or progression—the older patients in more advanced stages had more centralized cores. Our results indicate that CNMDU1 due to RYR1 mutation is a de facto core myopathy.
Elections, Ideology, and Turnover in the US Federal Government
Authors: Bolton Alexander , de Figueiredo John M , Lewis David E
Published: November 2020

A defining feature of public sector employment in the United States is the regular change in elected leadership. We describe how these changes alter policy and disrupt civil servants’ influence over agency decisions, potentially shaping their career choices. Using data on careers from over three million federal employees in the United States from 1988 to 2011, we evaluate how administration changes influence turnover in a series of regression analyses. We find substantial stability in the civil service but also some pockets of responsiveness to political factors, particularly among career senior executives in agencies with views divergent from the president’s. A combination of factors, including transitions, policy priorities, and ideological differences, could increase turnover propensity for these employees by nearly one-third in some agencies over an administration’s first term. This has implications for understanding possible mechanisms linking politics and organizational capacity and for understanding how and for whom politics is influential in career decisions.
Long-term results of definitive chemoradiotherapy for unresectable locally advanced esophageal squamous cell carcinoma
Authors: Ochi Masanori , Murakami Yuji , Nishibuchi Ikuno , Kubo Katsumaro , Imano Nobuki , Takeuchi Yuki , Kimura Tomoki , Hamai Yoichi , Emi Manabu , Okada Morihito , Nagata Yasushi
Published: November 2020

Purpose

The present study aimed to evaluate the long-term results of definitive chemoradiotherapy (CRT) for unresectable locally advanced esophageal squamous cell carcinoma (LA-ESCC).

Materials and methods

We analyzed eighty patients with unresectable LA-ESCC, who underwent definitive CRT between 2001 and 2014. The 5-year overall survival (OS), cause-specific survival (CSS), and progression-free survival (PFS) rates were calculated, and we investigated the prognostic factors and adverse events.

Results

The median age was 66 years (range, 41–83 years). Histologically, all patients had squamous cell carcinoma. The most common tumor site was the middle thoracic esophagus in 43 (54%) patients. According to the eighth edition of the Union for International Cancer Control TNM classification, sixty-six patients (83%) had T4 disease, 59 (74%) had regional lymph node (LN) metastases, and 35 (44%) had distant LN metastases beyond the regional LN (M1 LYM) disease. Forty-five (56%) and 35 (44%) patients belong to clinical stages IVA and IVB, respectively. The median follow-up period for survivors was 86 months. The 5-year OS, CSS, and PFS rates were 20.2%, 25.7%, and 18.4%, respectively. On univariate analysis, only the performance status score was significantly associated with better overall survival (p = 0.026). Grade 3 or higher late adverse events were observed in 12 (15%) patients, and these included cardiopulmonary adverse events in 6 (8%) patients. Treatment-related death occurred in 3 (4%) patients.

Conclusion

We showed the long-term results of definitive CRT for unresectable LA-ESCC. The survivals are still poor and new treatment strategies need to be developed.
External stoma diversion: a palliative measure for peristomal wound healing in resource-limited settings
Authors: Davis Rachel W , Sherif Youmna A , Morrison Catherine Anne
Published: November 2020

The provision of intestinal stoma care is challenging in austere settings due to limitations in surgical and wound care access as well as the high cost and sparsity of ostomy supplies. As a result, many surgical patients suffer from ostomy-related complications such as peristomal wounds and are unable to find relief for these complications from standard treatments and measures. This article describes the external stoma diversion, a cost-effective palliative surgical procedure that assists in the healing of peristomal wounds in resource-limited settings.
The B chromosome ofSorghum purpureosericeumreveals the first pieces of its sequence
Authors: Karafiátová Miroslava , Bednářová Martina , Said Mahmoud , Čížková Jana , Holušová Kateřina , Blavet Nicolas , Bartoš Jan
Published: November 2020

More than a century has passed since the B chromosomes were first discovered. Today we know much of their variability, morphology, and transmission to plant progeny. With the advent of modern technologies, B chromosome research has accelerated, and some of their persistent mysteries have since been uncovered. Building on this momentum, here we extend current knowledge of B chromosomes in Sorghum purpureosericeum to the sequence level. To do this, we estimated the B chromosome size at 421 Mb, sequenced DNA from flow-sorted haploid pollen nuclei of both B-positive (B+) and B-negative (B0) plants, and performed a repeat analysis on the Illumina raw sequence data. This analysis revealed nine putative B-specific clusters, which were then used to develop B chromosome-specific markers. Additionally, cluster SpuCL4 was identified and verified to be a centromeric repeat. We also uncovered two repetitive clusters (SpuCL168 and SpuCL115), which hybridized exclusively on the B chromosome under fluorescence in situ hybridization and can be considered as robust cytogenetic markers. Given that B chromosomes in Sorghum are rather unstable across all tissues, our findings could facilitate expedient identification of B+ plants and enable a wide range of studies to track this chromosome type in situ.
The proto-Nucleic Acid Builder: a software tool for constructing nucleic acid analogs
Authors: Alenaizan Asem , Barnett Joshua L , Hud Nicholas V , Sherrill C David , Petrov Anton S
Published: November 2020

The helical structures of DNA and RNA were originally revealed by experimental data. Likewise, the development of programs for modeling these natural polymers was guided by known structures. These nucleic acid polymers represent only two members of a potentially vast class of polymers with similar structural features, but that differ from DNA and RNA in the backbone or nucleobases. Xeno nucleic acids (XNAs) incorporate alternative backbones that affect the conformational, chemical, and thermodynamic properties of XNAs. Given the vast chemical space of possible XNAs, computational modeling of alternative nucleic acids can accelerate the search for plausible nucleic acid analogs and guide their rational design. Additionally, a tool for the modeling of nucleic acids could help reveal what nucleic acid polymers may have existed before RNA in the early evolution of life. To aid the development of novel XNA polymers and the search for possible pre-RNA candidates, this article presents the proto-Nucleic Acid Builder (https://github.com/GT-NucleicAcids/pnab), an open-source program for modeling nucleic acid analogs with alternative backbones and nucleobases. The torsion-driven conformation search procedure implemented here predicts structures with good accuracy compared to experimental structures, and correctly demonstrates the correlation between the helical structure and the backbone conformation in DNA and RNA.
Validation of human microRNA target pathways enables evaluation of target prediction tools
Authors: Kern Fabian , Krammes Lena , Danz Karin , Diener Caroline , Kehl Tim , Küchler Oliver , Fehlmann Tobias , Kahraman Mustafa , Rheinheimer Stefanie , Aparicio-Puerta Ernesto , Wagner Sylvia , Ludwig Nicole , Backes Christina , Lenhof Hans-Peter , von Briesen Hagen , Hart Martin , Keller Andreas , Meese Eckart
Published: November 2020

MicroRNAs are regulators of gene expression. A wide-spread, yet not validated, assumption is that the targetome of miRNAs is non-randomly distributed across the transcriptome and that targets share functional pathways. We developed a computational and experimental strategy termed high-throughput miRNA interaction reporter assay (HiTmIR) to facilitate the validation of target pathways. First, targets and target pathways are predicted and prioritized by computational means to increase the specificity and positive predictive value. Second, the novel webtool miRTaH facilitates guided designs of reporter assay constructs at scale. Third, automated and standardized reporter assays are performed. We evaluated HiTmIR using miR-34a-5p, for which TNF- and TGFB-signaling, and Parkinson's Disease (PD)-related categories were identified and repeated the pipeline for miR-7-5p. HiTmIR validated 58.9% of the target genes for miR-34a-5p and 46.7% for miR-7-5p. We confirmed the targeting by measuring the endogenous protein levels of targets in a neuronal cell model. The standardized positive and negative targets are collected in the new miRATBase database, representing a resource for training, or benchmarking new target predictors. Applied to 88 target predictors with different confidence scores, TargetScan 7.2 and miRanda outperformed other tools. Our experiments demonstrate the efficiency of HiTmIR and provide evidence for an orchestrated miRNA-gene targeting.
TonEBP recognizes R-loops and initiates m6A RNA methylation for R-loop resolution
Authors: Kang Hyun Je , Cheon Na Young , Park Hyun , Jeong Gyu Won , Ye Byeong Jin , Yoo Eun Jin , Lee Jun Ho , Hur Jin-Hoe , Lee Eun-A , Kim Hongtae , Lee Kyoo-young , Choi Soo Youn , Lee-Kwon Whaseon , Myung Kyungjae , Lee Ja Yil , Kwon Hyug Moo
Published: November 2020

R-loops are three-stranded, RNA–DNA hybrid, nucleic acid structures produced due to inappropriate processing of newly transcribed RNA or transcription-replication collision (TRC). Although R-loops are important for many cellular processes, their accumulation causes genomic instability and malignant diseases, so these structures are tightly regulated. It was recently reported that R-loop accumulation is resolved by methyltransferase-like 3 (METTL3)-mediated m6A RNA methylation under physiological conditions. However, it remains unclear how R-loops in the genome are recognized and induce resolution signals. Here, we demonstrate that tonicity-responsive enhancer binding protein (TonEBP) recognizes R-loops generated by DNA damaging agents such as ultraviolet (UV) or camptothecin (CPT). Single-molecule imaging and biochemical assays reveal that TonEBP preferentially binds a R-loop via both 3D collision and 1D diffusion along DNA in vitro. In addition, we find that TonEBP recruits METTL3 to R-loops through the Rel homology domain (RHD) for m6A RNA methylation. We also show that TonEBP recruits RNaseH1 to R-loops through a METTL3 interaction. Consistent with this, TonEBP or METTL3 depletion increases R-loops and reduces cell survival in the presence of UV or CPT. Collectively, our results reveal an R-loop resolution pathway by TonEBP and m6A RNA methylation by METTL3 and provide new insights into R-loop resolution processes.
How to limit the speed of a motor: the intricate regulation of the XPB ATPase and translocase in TFIIH
Authors: Kappenberger Jeannette , Koelmel Wolfgang , Schoenwetter Elisabeth , Scheuer Tobias , Woerner Julia , Kuper Jochen , Kisker Caroline
Published: November 2020

The superfamily 2 helicase XPB is an integral part of the general transcription factor TFIIH and assumes essential catalytic functions in transcription initiation and nucleotide excision repair. The ATPase activity of XPB is required in both processes. We investigated the interaction network that regulates XPB via the p52 and p8 subunits with functional mutagenesis based on our crystal structure of the p52/p8 complex and current cryo-EM structures. Importantly, we show that XPB’s ATPase can be activated either by DNA or by the interaction with the p52/p8 proteins. Intriguingly, we observe that the ATPase activation by p52/p8 is significantly weaker than the activation by DNA and when both p52/p8 and DNA are present, p52/p8 dominates the maximum activation. We therefore define p52/p8 as the master regulator of XPB acting as an activator and speed limiter at the same time. A correlative analysis of the ATPase and translocase activities of XPB shows that XPB only acts as a translocase within the context of complete core TFIIH and that XPA increases the processivity of the translocase complex without altering XPB’s ATPase activity. Our data define an intricate network that tightly controls the activity of XPB during transcription and nucleotide excision repair.
Plasma exchange for the management of ANCA-associated vasculitis: the con position
Authors: Specks Ulrich , Fussner Lynn A , Cartin-Ceba Rodrigo , Casal Moura Marta , Zand Ladan , Fervenza Fernando C
Published: November 2020

Advances in the diagnosis and treatment of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis have led to continued improvement in survival and prognosis over the course of the last 4 decades. Nevertheless, the most acute and severe disease manifestations, including severe kidney disease and alveolar hemorrhage, continue to be associated with increased early mortality from disease activity or treatment complications as well as risk for the development of end-stage kidney disease (ESKD), which in turn directly affects the overall prognosis of ANCA-associated vasculitis. Plasma exchange (PLEX) has long been proposed and used for these most severe disease manifestations under the assumption that its effects are swift and supported by our understanding of the pathogenic role of ANCA. Yet convincing evidence of a beneficial effect of PLEX in ANCA-associated vasculitis has been lacking, as early studies and small trials have generated conflicting results. The controversy regarding PLEX has been accentuated recently as the largest randomized controlled trial ever conducted in ANCA-associated vasculitis, the Plasma Exchange and Glucocorticoids in Severe ANCA-associated Vasculitis trial, which was specifically designed to evaluate the efficacy of PLEX in patients with severe renal disease or alveolar hemorrhage, failed to show a difference in the combined primary outcome measure of death or ESKD in patients who received PLEX versus those who did not. In light of these disappointing results, we herein review the currently available data on PLEX for ANCA-associated vasculitis and explain why we believe that these data no longer support the use of PLEX in ANCA-associated vasculitis.
Three-Month Pulmonary Function and Radiological Outcomes in COVID-19 Survivors: A Longitudinal Patient Cohort Study
Authors: Liao Xuejiao , Wang Ying , He Ziyi , Yun Yongxing , Hu Ming , Ma Zhenghua , Huang Ling , Cai Qingxian , Xu Lin , Hao Yuantao , Liu Lei
Published: November 2020

Background

This study aimed to investigate pulmonary function and radiological outcomes in a group of coronavirus disease 2019 (COVID-19) survivors.

Methods

One hundred seventy-two COVID-19 survivors in a follow-up clinic in a referral hospital underwent high-resolution computed tomography (CT) of the thorax and pulmonary function at 3 months after hospital discharge.

Results

The median duration from hospital discharge to radiological and pulmonary function test (interquartile range) was 90 (88–95) days. Abnormal pulmonary function was found in 11 (6.40%) patients, and abnormal small airway function (FEF25-75%) in 12 (6.98%). Six (3.49%) patients had obstructive ventilation impairment, and 6 (3.49%) had restrictive ventilatory impairment. No significant differences in lung function parameters were observed between the nonsevere and severe groups. Of 142 COVID-19 patients who underwent CT scan, 122 (85.91%) showed residual CT abnormalities and 52 (36.62%) showed chronic and fibrotic changes. The ground-glass opacities absorption in the lungs of severe cases was less satisfactory than that of nonsevere patients. The severe patients had higher CT scores than the nonsevere cases (2.00 vs 0.00; P < .001)

Conclusions

Of the COVID-19 survivors in our study, 6.40% still presented pulmonary function abnormality 3 months after discharge, which did not vary by disease severity during hospitalization; 85.91% of patients had abnormalities on chest CT, with fibrous stripes and ground-glass opacities being the most common patterns.
The Externalities of Corruption: Evidence from Entrepreneurial Firms in China*
Authors: Giannetti Mariassunta , Liao Guanmin , You Jiaxing , Yu Xiaoyun
Published: November 2020

Exploiting China’s anti-corruption campaign, we show that following a decrease in corruption, firm performance improves. Small and young firms benefit more. We identify the channels through which corruption hampers firm performance. Following the anti-corruption campaign, the allocation of capital and labor becomes more efficient. Firms operating in ex ante more corrupt environments experience larger productivity gains, higher growth of sales, and lower cost of debt than other firms. Taken together, our results suggest that corruption is an inefficient equilibrium for an economy because it creates negative externalities.
Medicating Anaesthesiology: Pharmaceutical Change, Specialisation and Healthcare Reform in Post-War Britain
Authors: Mueller Lucas M
Published: November 2020

This article examines how chemists, pharmacologists and anaesthetists developed the anaesthetic drug halothane and assessed the clinical use of the drug in the UK in the 1950s. I argue that halothane became seen as a superior drug not because of properties inherent in the new molecule CF3-CHClBr, but because anaesthetists used it to build a professional identity during a period of significant change in British medicine. The recently established National Health Service called for increasing the number of anaesthetists and other specialist hospital consultants. In this context, the specialist knowledge, novel technologies and new practices necessary for the safe usage of halothane enabled anaesthetists to forge a profession. The history of this process shows how professionalisation, pharmaceutical change and healthcare reform have interacted to shape knowledge transfer between laboratory and hospital with consequences for experimental ethics and patient safety.
Impact of storage conditions on protein oxidation of rendered by-product meals1
Authors: Frame Carl A , Huff-Lonergan Elisabeth J , Rossoni Serao Mariana C
Published: November 2020

Rendered products used in animal feed and pet food undergo extreme temperatures during manufacturing and may be stored up to 2 yr. No information is available on protein oxidation in these products. The objective of this study was to determine the extent to which typical antioxidant inclusion at different storage conditions may limit protein oxidation in typical rendered protein meals. Two experiments were conducted on 14 rendered products stored at either 45 °C for 7 or 14 d, or at 20 °C for 3 or 6 mo to determine the extent to which time, temperature, and antioxidants affect protein oxidation. Results from this study show that fish meal and chicken blood meal are susceptible to protein oxidation during storage at 45 °C (P = 0.05; 0.03) as well as during storage at 20 °C (P = 0.01; 0.04). Natural antioxidants were effective at limiting carbonyl formation in fish meal during short-term storage at 45 °C, whereas ethoxyquin was effective at limiting the extent of protein oxidation in fish meal stored long term at 20 °C.
Molecular Barcoding Reveals the Genus Streptomyces as Associated Root Endophytes of Apple (Malus domestica) Plants Grown in Soils Affected by Apple Replant Disease
Authors: Mahnkopp-Dirks Felix , Radl Viviane , Kublik Susanne , Gschwendtner Silvia , Schloter Michael , Winkelmann Traud
Published: November 2020

Apple replant disease (ARD) occurs when apple is repeatedly planted at the same site, leading to growth reductions and losses in fruit yield and quality. Up to now, the etiology has been poorly understood; however, soil (micro)biota are known to be involved. Because endophytes often colonize plants via the rhizosphere, this study aimed at comparing the bacterial endophytic root microbiome in plants growing in ARD-affected and unaffected soils from three different sites based on greenhouse biotests using a molecular barcoding approach. The initial endophytic microbiome of the starting material (in vitro propagated plants of the apple rootstock M26) did not significantly affect the overall richness and diversity of the endophytic community in plants after 8 weeks of growth in the respective soils but some genera of the initial microbiome managed to establish in apple roots. Proteobacteria was the dominant phylum in all samples. No differences in diversity or number of amplicon sequence variants (ASVs) between plants grown in ARD soil and unaffected soil was observed. However, several ASVs of high abundance uniquely found in plants grown in ARD-affected soils were Streptomyces spp. In soil from all three sites, these Streptomyces spp. were negatively correlated with plant growth parameters. Future inoculation experiments using selected Streptomyces isolates have to prove whether bacteria from this genus are opportunists or part of the ARD complex. For the first time, the bacterial endophytic community of apple roots grown in ARD-affected soils was characterized, which will help us to understand the etiology of ARD and develop countermeasures.

[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY 4.0 International license .
Spatial and Temporal Genetic Analyses ofPhyllosticta citricarpain Two Lemon Orchards in South Africa Reveal a Role of Asexual Reproduction Within Sexually Reproducing Populations
Authors: Carstens Elma , Linde Celeste C. , Fourie Paul H. , Bester-van der Merwe Aletta E. , Langenhoven Shaun D. , McLeod Adéle
Published: November 2020

Citrus black spot (CBS), caused by Phyllosticta citricarpa, is a disease that affects citrus worldwide. In different regions of the world where both mating types occur, reports differ as to whether asexually produced pycnidiospores play an important role in the epidemiology of CBS and fruit infections. Therefore, we investigated the potential role of pycnidiospores in two lemon orchards in South Africa by using microsatellite-based analysis of fruit populations over time (two seasons) and space (distance). The two orchards were situated in the semiarid North West province (NW) and subtropical Mpumalanga province (MP). Each population contained both mating types in 1:1 ratios, and linkage disequilibrium analysis indicated a random mating population. A total of 109 and 94 multilocus genotypes (MLGs) were detected across the two seasons in the NW and MP orchards, respectively. Psexanalyses indicated that most MLGs probably resulted from sexual reproduction, but there were six predominant MLGs in each orchard that were probably replicated via asexual reproduction. Each of the predominant MLGs was monomorphic for mating type. In the NW, five predominant and widespread MLGs caused 46 and 44% of the fruit infections in the two seasons, whereas in MP, three MLGs caused 34 and 48% of the infections. Asexual reproduction in both orchards was supported by low MLG evenness values in all populations. In both orchards, distance was not a reliable predictor of population genetic substructuring or season. Populations of P. citricarpa in the MP and NW orchards were significantly genetically differentiated from each other.
Association between gastrointestinal symptoms and depression among older adults in Taiwan: A cross-sectional study
Authors: Huang Mao-Hsuan , Wang Yen-Po , Wu Po-Shan , Chan Yee-Lam E. , Cheng Chih-Ming , Yang Cheng-Hung , Tsai Shih-Jen , Lu Ching-Liang , Tsai Chia-Fen
Published: November 2020

Background:

Older adults with depression more frequently experience somatic and gastrointestinal (GI) problems compared with people without depression and younger adults with depression. However, whether GI symptoms are predictive of elevated rates of depression among older adults is unclear.

Methods:

We enrolled 106 older adults (>60 years old); 69 had late-life depression (LLD), and 37 were controls. All participants gave ratings on the Gastrointestinal Symptom Rating Scale (GSRS) and Hamilton Depression Rating Scale. Food consumption was assessed using a food frequency questionnaire, and a Mediterranean diet score was used as a covariate.

Results:

Compared with the controls, patients with LLD reported higher levels of depressive and GI symptoms and reported more reflux, abdominal pain, and dyspepsia symptoms, and these symptoms were correlated with Hamilton Depression Rating Scale scores (GSRS total: β = 0.47; reflux: β = 1.47; abdominal pain: β = 1.98; dyspepsia: β = 1.02; all p < 0.01). After demographic variables and Mediterranean diet score were controlled for, a logistic regression analysis indicated that total GSRS score was an independent determinant of LLD (odds ratio: 1.20, 95% CI: 1.04-1.38). Moreover, a stratified analysis by depression severity indicated that higher total GSRS score may contribute to greater depression severity (odds ratio: 1.25, 95% CI: 1.04-1.52).

Conclusion:

We provide evidence that GI symptoms are associated with depressive symptoms among patients with LLD. Older people with more specific GI symptoms, such as reflux, abdominal pain, and dyspepsia, are potentially at greater risk of having LLD.
Skin Cancer, Back to Basics
Authors: Davis Kyleen E.
Published: November 2020

Actinic keratoses (AKs) are rough, scaly papules or plaques on sun-exposed areas of the body that may progress to squamous cell carcinoma. AKs are extremely common, with the highest incidence in individuals living close to the equator. Risk factors for AKs include advanced age, fair skin, male gender, baldness in men, immunosuppression, and chronic sun exposure. Many effective therapies for individual AKs exist; however, underlying field cancerization—a mix of clinical and subclinical lesions—must be addressed for treatment to be successful. Nurses can play a pivotal role in empowering and educating their patients to make the right choices to keep their skin healthy and cancer-free for years to come.
Brain Development in Infants of Mothers With Gestational Diabetes Mellitus: A Diffusion Tensor Imaging Study
Authors: Xuan De-Sheng , Zhao Xin , Liu Yan-Chao , Xing Qing-Na , Shang Hong-Lei , Zhu Pei-Ying , Zhang Xiao-An
Published: November 2020

Objective

The objective of this study was to investigate clinical neurocognitive performance and microstructural white matter (WM) alterations in infants of mothers with gestational diabetes mellitus (GDM) using diffusion tensor imaging.

Materials and Methods

Infants (corrected gestational age, 33.42–36.00 weeks) of mothers with GDM (n = 31) and gestational age- and sex-matched unexposed controls (n = 31) accomplished 3-T diffusion tensor imaging scans and neurocognitive tests. Diffusion tensor imaging measures, mainly referring to fractional anisotropy (FA) values, were compared between 2 groups, and within-group analysis of correlation between FA values and neurocognitive testing outcomes in GDM-exposed infants was conducted subsequently.

Results

Fractional anisotropy was significantly decreased in the splenium of corpus callosum, posterior limb of internal capsule, thalamus in infants of mothers with GDM when compared with controls (P < 0.05), reflecting microstructural WM abnormalities in the GDM group. Decreased FA was associated with worse neurocognitive performance in the exposed group (P < 0.05).

Conclusions

Individuals of mothers with GDM showed microstructural WM abnormalities in different brain regions, which were significantly related to worse neurocognitive performance. This might reveal that GDM directly insults the brain development of the offspring.
Independent Dentists in the UK have less access to Occupational Health
Authors: Ranka Meena Satish , Ranka Satish
Published: November 2020

Objectives

Respiratory illnesses like Severe Acute Respiratory Syndrome, Middle East Respiratory Syndrome and the current SARS-CoV-2 virus pandemic are transmitted by respiratory droplets. Certain dental procedures generate aerosols, one of the highest sources of transmission of droplet infections. During the current pandemic, dentists in the UK were initially restricted in their work and now have guidance from NHS England and the Chief Dental Officer for the full resumption of safe and effective routine dental care to patients. Lack of work, impact on income and working in the continual pandemic situation are likely to cause significant mental stress in dentists. Occupational health (OH) can have a vital role to help such dentists remain in work by advising strategies to cope with stress and offering timely evidence-based interventions and adjustments. The aim was to assess if the dentists in the UK had access to OH and whether access to the OH services helped.

Methods

A survey link was sent to 200 dentists in the UK after the peak of the current pandemic.

Results

124 dentists responded to the survey. The response rate was 62%. 59% of the dentists in the survey did not have access to OH services in their workplace. Only 15% of dentists working in the independent sector had access to OH services compared to 78% working in the NHS or having NHS contracts. None of the dentists in the survey accessed OH services.

Conclusions

Access to OH services for the dentists needs improvement, particularly in the Independent sector in the UK.

Article Summary

Strengths and limitations of the study:

Sample representative of the population studied.

No observer subjectivity

Precise results

Inflexible design, no control group and lack of random sampling
A model of endemic coronavirus infections
Authors: Huen David S.
Published: November 2020

This work proposes that epidemiological features of both endemic coronaviruses and the recent highly pathogenic outbreak coronaviruses can be combined within an integrated framework. In this framework, mortality amongst those infected for the first time is mostly amongst the old but survivors acquire fatal infection immunity (FII). Subjects with FII can subsequently be infected and infect others without suffering significant mortality. Under these conditions, coronaviruses induce endemic infections that elicit FII in individuals during childhood when the risk of mortality is low and maintain it throughout their lifetime, thereby protecting the population against the worst effects of infection.

A multi-compartment ODE model was constructed to explore the implications of this proposal on the evolution of a zoonosis sharing properties of both SARS-CoV-2 and endemic coronaviruses. The results show that mortality has two components, the first incurred during transition to endemicity and the other is exacted on a continuing basis. The relative contribution of each depends on the longevity of the FII state. In particular, a one-time vaccination of the older subpopulation is sufficient to reduce total mortality if FII is long-lived. The effect of a regular vaccination was also examined when FII was shorter lived. Herd immunity was not achieved.

The validity of this proposal with regard to Covid-19 depends on whether reinfection with SARS-CoV-2 behaves in the manner expected of FII. If it does, then certain considerations apply to how Covid-19 is to be managed and how vaccine choice could influence that.
A time-resolved proteomic and diagnostic map characterizes COVID-19 disease progression and predicts outcome
Authors: Demichev Vadim , Tober-Lau Pinkus , Nazarenko Tatiana , Thibeault Charlotte , Whitwell Harry , Lemke Oliver , Röhl Annika , Freiwald Anja , Szyrwiel Lukasz , Ludwig Daniela , Correia-Melo Clara , Helbig Elisa T. , Stubbemann Paula , Grüning Nana-Maria , Blyuss Oleg , Vernardis Spyros , White Matthew , Messner Christoph B. , Joannidis Michael , Sonnweber Thomas , Klein Sebastian J. , Pizzini Alex , Wohlfarter Yvonne , Sahanic Sabina , Hilbe Richard , Schaefer Benedikt , Wagner Sonja , Mittermaier Mirja , Machleidt Felix , Garcia Carmen , Ruwwe-Glösenkamp Christoph , Lingscheid Tilman , de Jarcy Laure Bosquillon , Stegemann Miriam S. , Pfeiffer Moritz , Jürgens Linda , Denker Sophy , Zickler Daniel , Enghard Philipp , Zelezniak Aleksej , Campbell Archie , Hayward Caroline , Porteous David J. , Marioni Riccardo E. , Uhrig Alexander , Müller-Redetzky Holger , Zoller Heinz , Löffler-Ragg Judith , Keller Markus A. , Tancevski Ivan , Timms John F. , Zaikin Alexey , Hippenstiel Stefan , Ramharter Michael , Witzenrath Martin , Suttorp Norbert , Lilley Kathryn , Mülleder Michael , Sander Leif Erik ,   PA-COVID-19 Study group, Ralser Markus , Kurth Florian
Published: November 2020

COVID-19 is highly variable in its clinical presentation, ranging from asymptomatic infection to severe organ damage and death. There is an urgent need for predictive markers that can guide clinical decision-making, inform about the effect of experimental therapies, and point to novel therapeutic targets. Here, we characterize the time-dependent progression of COVID-19 through different stages of the disease, by measuring 86 accredited diagnostic parameters and plasma proteomes at 687 sampling points, in a cohort of 139 patients during hospitalization. We report that the time-resolved patient molecular phenotypes reflect an initial spike in the systemic inflammatory response, which is gradually alleviated and followed by a protein signature indicative of tissue repair, metabolic reconstitution and immunomodulation. Further, we show that the early host response is predictive for the disease trajectory and gives rise to proteomic and diagnostic marker signatures that classify the need for supplemental oxygen therapy and mechanical ventilation, and that predict the time to recovery of mildly ill patients. In severely ill patients, the molecular phenotype of the early host response predicts survival, in two independent cohorts and weeks before outcome. We also identify age-specific molecular response to COVID-19, which involves increased inflammation and lipoprotein dysregulation in older patients. Our study provides a deep and time resolved molecular characterization of COVID-19 disease progression, and reports biomarkers for risk-adapted treatment strategies and molecular disease monitoring. Our study demonstrates accurate prognosis of COVID-19 outcome from proteomic signatures recorded weeks earlier.
Diagnosis and Tracking of SARS-CoV-2 Infection By T-Cell Receptor Sequencing
Authors: Gittelman Rachel M. , Lavezzo Enrico , Snyder Thomas M. , Zahid H. Jabran , Elyanow Rebecca , Dalai Sudeb , Kirsch Ilan , Baldo Lance , Manuto Laura , Franchin Elisa , Vecchio Claudia Del , Pacenti Monia , Boldrin Caterina , Cattai Margherita , Saluzzo Francesca , Padoan Andrea , Plebani Mario , Simeoni Fabio , Bordini Jessica , Lorè Nicola I. , Lazarevic Dejan , Cirillo Daniela M. , Ghia Paolo , Toppo Stefano , Carlson Jonathan M. , Robins Harlan S. , Tonon Giovanni , Crisanti Andrea
Published: November 2020

In viral diseases T cells exert a prominent role in orchestrating the adaptive immune response and yet a comprehensive assessment of the T-cell repertoire, compared and contrasted with antibody response, after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is currently lacking. A prior population-scale study of the municipality of Vo’, Italy, conducted after the initial SARS-CoV-2 outbreak uncovered a high frequency of asymptomatic infected individuals and their role in transmission in this town. Two months later, we sampled the same population’s T-cell receptor repertoire structure in terms of both diversity (breadth) and frequency (depth) to SARS-CoV-2 antigens to identify associations with both humoral response and protection. For this purpose, we analyzed T-cell receptor and antibody signatures from over 2,200 individuals, including 76 PCR-confirmed SARS-CoV-2 cases (25 asymptomatic, 42 symptomatic, 9 hospitalized). We found that 97.4% (74/76) of PCR confirmed cases had elevated levels of T-cell receptors specific for SARS-CoV-2 antigens. The depth and breadth of the T-cell receptor repertoire were both positively associated with neutralizing antibody titers; helper CD4+ T cells directed towards viral antigens from spike protein were a primary factor in this correlation. Higher clonal depth of the T-cell response to the virus was also significantly associated with more severe disease course. A total of 40 additional suspected infections were identified based on T-cell response from the subjects without confirmatory PCR tests, mostly among those reporting symptoms or having household exposure to a PCR-confirmed infection. Taken together, these results establish that T cells are a sensitive, reliable and persistent measure of past SARS-CoV-2 infection that are differentially activated depending on disease morbidity.
Genetic analyses of gynecological disease identify genetic relationships between uterine fibroids and endometrial cancer, and a novel endometrial cancer genetic risk region at the WNT4 1p36.12 locus
Authors: Kho Pik Fang , Mortlock Sally ,   Endometrial Cancer Association Consortium,   International Endometriosis Genetics Consortium, Rogers Peter A.W. , Nyholt Dale R. , Montgomery Grant W. , Spurdle Amanda B. , Glubb Dylan M. , O’Mara Tracy A.
Published: November 2020

Endometriosis, polycystic ovary syndrome (PCOS) and uterine fibroids have been proposed as endometrial cancer risk factors; however, disentangling their relationships with endometrial cancer is complicated due to shared risk factors and comorbidities. Using genome-wide association study (GWAS) data, we explored the relationships between these non-cancerous gynecological diseases and endometrial cancer risk by assessing genetic correlation, causal relationships and shared risk loci. We found significant genetic correlation between endometrial cancer and PCOS, and uterine fibroids. Adjustment for genetically predicted body mass index (a risk factor for PCOS, uterine fibroids and endometrial cancer) substantially attenuated the genetic correlation between endometrial cancer and PCOS but did not affect the correlation with uterine fibroids. Mendelian randomization analyses provided evidence of a causal relationship between only uterine fibroids and endometrial cancer. Gene-based analyses revealed risk regions shared between endometrial cancer and endometriosis, and uterine fibroids. Multi-trait GWAS analysis of endometrial cancer and the genetically correlated gynecological diseases identified a novel genome-wide significant endometrial cancer risk locus at 1p36.12, which replicated in an independent endometrial cancer dataset. Interrogation of functional genomic data at 1p36.12 revealed biologically relevant genes, including WNT4 which is necessary for the development of the female reproductive system. In summary, our study provides genetic evidence for a causal relationship between uterine fibroids and endometrial cancer. It further provides evidence that the comorbidity of endometrial cancer, PCOS and uterine fibroids may partly be due to shared genetic architecture. Notably, this shared architecture has revealed a novel genome-wide risk locus for endometrial cancer.
Public participation in crisis policymaking. How 30,000 Dutch citizens advised their government on relaxing COVID-19 lockdown measures
Authors: Mouter Niek , Hernandez Jose Ignacio , Itten Anatol Valerian
Published: November 2020

Following the outbreak of COVID-19, governments took unprecedented measures to curb the spread of the virus. Public participation in decisions regarding (the relaxation of) these measures has been notably absent, despite being recommended in the literature. Here, as one of the exceptions, we report the results of 30,000 citizens advising the government on eight different possibilities for relaxing lockdown measures in the Netherlands. By making use of the novel method Participatory Value Evaluation (PVE), participants were asked to recommend which out of the eight options they prefer to be relaxed. Participants received information regarding the societal impacts of each relaxation option, such as the impact of the option on the healthcare system. The results of the PVE informed policymakers about people’s preferences regarding (the impacts of) the relaxation options. For instance, we established that participants assign an equal value to a reduction of 100 deaths among citizens younger than 70 years and a reduction of 168 deaths among citizens older than 70 years. We show how these preferences can be used to rank options in terms of desirability. Citizens advised to relax lockdown measures, but not to the point at which the healthcare system becomes heavily overloaded. We found wide support for prioritising the re-opening of contact professions. Conversely, participants disfavoured options to relax restrictions for specific groups of citizens as they found it important that decisions lead to “unity” and not to “division”. 80% of the participants state that PVE is a good method to let citizens participate in government decision-making on relaxing lockdown measures. Participants felt that they could express a nuanced opinion, communicate arguments, and appreciated the opportunity to evaluate relaxation options in comparison to each other while being informed about the consequences of each option. This increased their awareness of the dilemmas the government faces.