bluuebunny/crossref_metadata_2025 huggingface dataset:
Extraintestinal Manifestations and Other Comorbidities in Ulcerative Colitis and Crohn Disease: A Danish Nationwide Registry Study 2003–2016
Authors: Vadstrup Kasper , Alulis Sarah , Borsi Andras , Jørgensen Tine Rikke , Nielsen Agnete , Munkholm Pia , Qvist Niels
Published: August 2020

Background

Extraintestinal manifestations (EIMs) in inflammatory bowel disease (IBD) may be a frequent complication to an underlying abnormal immune response. This study investigated the occurrence of EIMs in Crohn disease (CD) and ulcerative colitis (UC) patients using population-based data in Denmark from 2003 to 2016.

Methods

In this national registry-based study, incident CD and UC patients between 2003 and 2015 were matched on age and gender with non-IBD controls and followed until 2016. The selected EIMs for this study included 51 different diagnoses divided into biological systems of diseases, which were tested for differences in the timing and occurrence of EIMs.

Results

The study cohort included 10,302 patients with CD and 22,144 patients with UC. The highest risk of patients experiencing EIM/comorbidities for the first time before their IBD diagnosis was in the skin and intestinal tract systems. For CD, the odds ratio of having an EIM before or after IBD diagnosis, as compared with controls, was significant in the skin, intestinal tract, hepatopancreatobiliary, musculoskeletal, ocular, renal, and respiratory systems. For UC, the risks were similar before and after UC diagnosis, apart from the nervous system where the odds ratio was significantly higher before the diagnosis of UC, and significantly lower after diagnosis for diseases in the ocular system.

Conclusions

EIMs in CD and UC patients may also precede their IBD diagnosis. These findings may indicate a significant diagnostic delay of CD and UC, and the occurrence of known EIMs should prompt physicians to look for patients possibly having underlying IBD.
The JAK1/3 Inhibitor to Tofacitinib Suppresses T Cell Homing and Activation in Chronic Intestinal Inflammation
Authors: Gerlach Katharina , Lechner Kristina , Popp Vanessa , Offensperger Laura , Zundler Sebastian , Wiendl Maximilian , Becker Emily , Atreya Raja , Rath Timo , Neurath Markus F , Weigmann Benno
Published: August 2020

Background and Aims

The molecular mechanism of action of the Janus kinase [JAK] inhibitor tofacitinib is poorly understood.

Methods

Here we analysed the inhibitory effect of tofacitinib on mucosal and blood T cells from patients with ulcerative colitis [UC]. Furthermore, tofacitinib treatment was analysed in experimental colitis models and wound healing. Additionally, tofacitinib effects were analysed in bioassays.

Results

Tofacitinib significantly reduced T cell-derived inflammatory cytokine production [Th2, Th9, Th17] in patients with active UC. Additionally, impaired expression of the homing receptors alpha4/beta1 and alpha4/beta7, as well as reduced gut homing capacity of T cells in a humanised mouse model of colitis, were observed. Tofacitinib suppressed acute and chronic oxazolone colitis, compared with untreated wild-type mice, associated with downregulation of cytokines produced by Th2, Th9, and Th17 cells. Functionally, tofacitinib induced apoptosis of intestinal epithelial cells and prevented mucosal wound healing in vivo at higher concentration. Thus, our findings suggest that tofacitinib is quite effective in protecting from colitis, by inhibition of a bundle of T cell-derived cytokines like IL-5, IL-6, IL-9, IL-13, and IL-17A.

Conclusions

Application of tofacitinib emerges as an attractive concept for treatment of chronic intestinal inflammation at lower concentrations, whereas higher concentrations require attention due to prolonged wound healing.

Podcast

This article has an associated podcast which can be accessed at https://academic.oup.com/ecco-jcc/pages/podcast
Impact of Hemlock Woolly Adelgid (Hemiptera: Adelgidae) Infestation on the Jasmonic Acid-Elicited Defenses of Tsuga canadensis (Pinales: Pinaceae)
Authors: Rigsby Chad M , Kinahan Ian G , May Amelia , Kostka Amy , Houseman Nick , Savage Suzanne K , Whitney Elizabeth R , Preisser Evan L
Published: August 2020

Hemlock woolly adelgid is an invasive piercing-sucking insect in eastern North America, which upon infestation of its main host, eastern hemlock (‘hemlock’), improves attraction and performance of folivorous insects on hemlock. This increased performance may be mediated by hemlock woolly adelgid feeding causing antagonism between the the jasmonic acid and other hormone pathways. In a common garden experiments using hemlock woolly adelgid infestation and induction with methyl jasmonate (MeJA) and measures of secondary metabolite contents and defense-associated enzyme activities, we explored the impact of hemlock woolly adelgid feeding on the local and systemic induction of jasmonic acid (JA)-elicited defenses. We found that in local tissue hemlock woolly adelgid or MeJA exposure resulted in unique induced phenotypes, whereas the combined treatment resulted in an induced phenotype that was a mixture of the two individual treatments. We also found that if the plant was infested with hemlock woolly adelgid, the systemic response of the plant was dominated by hemlock woolly adelgid, regardless of whether MeJA was applied. Interestingly, in the absence of hemlock woolly adelgid, hemlock plants had a very weak systemic response to MeJA. We conclude that hemlock woolly adelgid infestation prevents systemic induction of JA-elicited defenses. Taken together, compromised local JA-elicited defenses combined with weak systemic induction could be major contributors to increased folivore performance on hemlock woolly adelgid-infested hemlock.
The Attraction of Amazonian Dung Beetles (Coleoptera: Scarabaeidae: Scarabaeinae) to the Feces of Omnivorous Mammals Is Dependent on Their Diet: Implications for Ecological Monitoring
Authors: Ferreira Kleyton R , Puker Anderson , Correa César M A
Published: August 2020

The immense sampling effort used in ecological research on dung beetles (Coleoptera: Scarabaeidae: Scarabaeinae) has required large amounts of human feces to conduct experiments in the field. Thus, the amount of human feces available can be an important limiting factor for research. Therefore, dung from large omnivorous mammals, such as pig, has been used to reduce this limitation. Here, we evaluated how the type of diet can influence the attractiveness of omnivorous-mammal feces to Amazonian dung beetles. We sampled dung beetles in 10 fragments of Amazon rainforest in July 2018 (dry season) and March 2019 (rainy season), using pitfall traps baited with swill pig dung (household waste-based diet), grain pig dung (maize+soybean-based diet), and human feces (control) in Juína, Mato Grosso, Brazil. In all, 2,080 individuals from 51 species of dung beetles were collected. Between the pig dung evaluated, higher total abundance and species richness was captured with grain pig dung. However, the species composition and community structure were similar between pig dung types. Additionally, grain pig dung captured total species richness, species composition, and structure similar to that for human feces. Thus, although grain pig dung did not sample total abundance similar to human feces, this type of dung can be efficient for an accurate survey of the total species richness, species composition, and structure of dung beetles in the Amazon rainforest.
The pandemic predominantly hits poor neighbourhoods? SARS-CoV-2 infections and COVID-19 fatalities in German districts
Authors: Plümper Thomas , Neumayer Eric
Published: August 2020

Background

Reports from the UK and the USA suggest that coronavirus disease 2019 (COVID-19) predominantly affects poorer neighbourhoods. This article paints a more complex picture by distinguishing between a first and second phase of the pandemic. The initial spread of infections and its correlation with socio-economic factors depends on how the virus first entered a country. The second phase of the pandemic begins when individuals start taking precautionary measures and governments implement lockdowns. In this phase, the spread of the virus depends on the ability of individuals to socially distance themselves, which is to some extent socially stratified.

Methods

We analyze the geographical distribution of known cumulative cases and fatalities per capita in an ecological analysis across local districts in Germany distinguishing between the first and the second phase of the pandemic.

Results

In Germany, the virus first entered via individuals returning from skiing in the Alps and other international travel. In this first phase, we find a positive association between the wealth of a district and infection rates and a negative association with indicators of social deprivation. During the second phase and controlling for path dependency, districts with a higher share of university-educated employees record fewer new infections and deaths and richer districts record fewer deaths, districts with a higher unemployment rate record more deaths.

Conclusions

The social stratification of COVID-19 changes substantively across the two phases of the pandemic in Germany. Only in the second phase and controlling for temporal dependence does COVID-19 predominantly hit poorer districts.
Understanding the Metabolic Capacity of Antarctic Fishes to Acclimate to Future Ocean Conditions
Authors: Todgham Anne E , Mandic Milica
Published: August 2020

Synopsis

Antarctic fishes have evolved under stable, extreme cold temperatures for millions of years. Adapted to thrive in the cold environment, their specialized phenotypes will likely render them particularly susceptible to future ocean warming and acidification as a result of climate change. Moving from a period of stability to one of environmental change, species persistence will depend on maintaining energetic equilibrium, or sustaining the increased energy demand without compromising important biological functions such as growth and reproduction. Metabolic capacity to acclimate, marked by a return to metabolic equilibrium through physiological compensation of routine metabolic rate (RMR), will likely determine which species will be better poised to cope with shifts in environmental conditions. Focusing on the suborder Notothenioidei, a dominant group of Antarctic fishes, and in particular four well-studied species, Trematomus bernacchii, Pagothenia borchgrevinki, Notothenia rossii, and N. coriiceps, we discuss metabolic acclimation potential to warming and CO2-acidification using an integrative and comparative framework. There are species-specific differences in the physiological compensation of RMR during warming and the duration of acclimation time required to achieve compensation; for some species, RMR fully recovered within 3.5 weeks of exposure, such as P. borchgrevinki, while for other species, such as N. coriiceps, RMR remained significantly elevated past 9 weeks of exposure. In all instances, added exposure to increased PCO2, further compromised the ability of species to return RMR to pre-exposure levels. The period of metabolic imbalance, marked by elevated RMR, was underlined by energetic disturbance and elevated energetic costs, which shifted energy away from fitness-related functions, such as growth. In T. bernacchii and N. coriiceps, long duration of elevated RMR impacted condition factor and/or growth rate. Low growth rate can affect development and ultimately the timing of reproduction, severely compromising the species’ survival potential and the biodiversity of the notothenioid lineage. Therefore, the ability to achieve full compensation of RMR, and in a short-time frame, in order to avoid long term consequences of metabolic imbalance, will likely be an important determinant in a species’ capacity to persist in a changing environment. Much work is still required to develop our understanding of the bioenergetics of Antarctic fishes in the face of environmental change, and a targeted approach of nesting a mechanistic focus in an ecological and comparative framework will better aid our predictions on the effect of global climate change on species persistence in the polar regions.
Wall-Crossing for Newton–Okounkov Bodies and the Tropical Grassmannian
Authors: Escobar Laura , Harada Megumi
Published: August 2020

Tropical geometry and the theory of Newton–Okounkov bodies are two methods that produce toric degenerations of an irreducible complex projective variety. Kaveh and Manon showed that the two are related. We give geometric maps between the Newton–Okounkov bodies corresponding to two adjacent maximal-dimensional prime cones in the tropicalization of $X$. Under a technical condition, we produce a natural “algebraic wall-crossing” map on the underlying value semigroups (of the corresponding valuations). In the case of the tropical Grassmannian $Gr(2,m)$, we prove that the algebraic wall-crossing map is the restriction of a geometric map. In an appendix by Nathan Ilten, he explains how the geometric wall-crossing phenomenon can also be derived from the perspective of complexity-one $T$-varieties; Ilten also explains the connection to the “combinatorial mutations” studied by Akhtar–Coates–Galkin–Kasprzyk.
Supplementing Ca salts of soybean oil to late-gestating beef cows: impacts on performance and physiological responses of the offspring
Authors: Brandão Alice Poggi , Cooke Reinaldo F , Schubach Kelsey M , Rett Bruna , Souza Osvaldo A , Schachtschneider Christopher L , Perry George A , Arispe Sergio A , Jump Donald B , Pohler Ky G , Bohnert David W , Marques Rodrigo S
Published: August 2020

This experiment compared the performance and physiological responses of the offspring from cows supplemented with Ca salts of soybean oil (CSSO) or prilled saturated fat (CON) during late gestation. Nonlactating, pregnant, multiparous Angus × Hereford cows (n = 104) that conceived during the same fixed-time artificial insemination protocol were assigned to this experiment. Cows were ranked by pregnancy sire (one of two sires), body weight (BW), and body condition score (BCS) on day −15 of the experiment (day 180 of gestation). Cows were then assigned to receive (dry matter basis) 415 g of soybean meal per cow daily in addition to: 1) 195 g/cow daily of CSSO (n = 52) or 2) 170 g/cow daily of CON (n = 52). Cows were maintained in two pastures (26 cows/treatment per pasture) and received daily 12.7 kg/cow (dry matter basis) of grass-alfalfa hay from day −15 to calving. Cows were segregated into 1 of 24 feeding pens three times weekly and received treatments individually from day 0 to calving. Calves were weaned on day 290 of the experiment, preconditioned for 35 d (day 291 to 325), and transferred to a feedyard, where they remained until slaughter (day 514). Cows receiving CSSO and their calves had greater (P < 0.01) plasma concentrations of linoleic acid and total ω-6 PUFA compared with CON after calving. Concentrations of immunoglobulin G in the colostrum and in calf plasma 24 h after birth were greater (P ≤ 0.02) in CSSO vs. CON cattle. Calves from CSSO cows had greater (P ≤ 0.05) expression of adipogenic (adipocyte fatty acid-binding protein and stearoyl-CoA desaturase) and myogenic (myogenic differentiation 1 and myogenin) genes in the longissimus muscle (LM) compared with CON. No treatment differences in birth BW, weaning BW, and final preconditioning BW were noted (P ≥ 0.36). Average daily gain and final BW in the feedyard were greater (P ≤ 0.05) in steers from CSSO cows compared with CON. The incidence of calves diagnosed with BRD that required a second antimicrobial treatment was less (P = 0.03) in calves from CSSO cows, resulting in reduced (P = 0.05) need of treatments to regain health compared with CON. Upon slaughter, LM area was greater (P = 0.03) in calves from CSSO cows compared with CON. Collectively, these results are indicative of programming effects on postnatal offspring growth and health resultant from CSSO supplementation to late-gestating cows. Hence, supplementing CSSO to beef cows during pregnancy might be a feasible alternative to optimize offspring productivity and welfare.
Sap Beetles (Coleoptera: Nitidulidae) in Oak Forests of Two Northeastern States: A Comparison of Trapping Methods and Monitoring for Phoretic Fungi
Authors: DiGirolomo Marc F , Munck Isabel A , Dodds Kevin J , Cancelliere Jessica
Published: August 2020

Oak wilt is slowly expanding in the northeastern United States. Several nitidulid beetle species are known vectors of the fungus [Bretziella fagacearum (Bretz) Z. W. De Beer, Marinc., T. A. Duong, and M. J. Wingf (Microascales: Ceratocystidaceae)] that causes this disease, acquiring spores from fungal mats on infected trees and transmitting them to uninfected trees. Survey and fungal isolation from captured nitidulid beetles could be an important tool for detecting the presence of this disease in a geographic area not previously known to have oak wilt. In preparation for monitoring activities in such areas, two trapping studies were conducted in the northeastern United States: 1) trap test comparing the efficacy of wind-oriented pipe, multiple-funnel, and modified pitfall traps for nitidulids and 2) wet and dry collection cup comparison. Lures were a combination of nitidulid pheromones and fermenting liquid. Results support the use of multiple-funnel traps over the other two trap types, for both targeted species-specific surveys and community sampling. More total nitidulids, Colopterus truncatus (Randall), and Glischrochilus fasciatus (Olivier) were captured in wet collection cups compared with dry cups. Twenty-seven fungal species were isolated, none of which were B. fagacearum. Many fungi isolated from beetles were plant pathogens, indicating that in addition to the oak wilt fungus, sap beetles may contribute to the spread of other plant diseases.
Performance of a Low-Cost Acoustic Insect Detector System with Sitophilus oryzae (Coleoptera: Curculionidae) in Stored Grain and Tribolium castaneum (Coleoptera: Tenebrionidae) in Flour
Authors: Mankin R W , Jetter E , Rohde B , Yasir M
Published: August 2020

Reduction of postharvest losses is gaining increased priority in warm regions where insect infestation may cause rapid deterioration of staple commodities. Acoustic detection can be used to assess the likelihood of insect infestations in bags of grain, flour, and other commodities that are stored in small holdings in developing countries, enabling rapid targeting of treatments. A portable postharvest insect detection system was developed with the goal to provide low-cost capability to acoustically assess infestations in small-scale storage facilities. Electret microphones input pest insect sounds to a 32-bit microcontroller platform that digitized and stored the signals on a digital memory card transferable to a portable laptop computer. The insect sounds then were analyzed by custom-written software that matched their spectra to those of known pests. Infestations of Sitophilus oryzae (L) in 2.6-kg bags could be detected down to densities of 1.9 adults/kg in grain and Tribolium castaneum (Herbst) down to 3.8 adults/kg in flour in laboratory settings. Also, differences in the rates of sounds per insect in treatments with different numbers ranging from 5 to 50 insects suggested that the sound rates of adults of different species at different population densities may be noticeably affected by aggregation pheromones or other behaviorally active semiochemicals. Further testing is needed but previous experience with acoustic detection systems suggests that the prototype has potential for use in small storage facilities where early detection of infestations is difficult to provide.
The Quest for a European Safe Asset—A Comparative Legal Analysis of Sovereign Bond-Backed Securities, E-Bonds, Purple Bonds, and Coronabonds
Authors: Grund Sebastian
Published: August 2020

The European sovereign debt crisis and, more recently, the COVID-19 pandemic have revealed the European Economic and Monetary Union’s fragility, which essentially emanates from the inherent tension between a single monetary policy and decentralized fiscal policies. To cushion economic and financial shocks and sever the sovereign-bank doom loop, different proposals to create a common public debt security have been put forward, although none of them has so far seen the light of day. Building on pertinent economic and finance scholarship, this article reviews four promising safe asset proposals from a legal perspective: Sovereign bond-backed securities (SBBS), E-bonds, Purple bonds, and Coronabonds. Rather than focusing on their feasibility under EU law or national constitutional law, this article compares the proposals from an investor perspective against the backdrop of the following formal and functional legal characteristics that render assets ‘safe’: governing law, dispute settlement forum, investor protection, and investor representation in sovereign debt restructurings. Against this backdrop, targeted recommendations on critical design elements of safe assets, with the aim of reconciling the economic policy objectives with the pertinent legal constraints, are advanced.
Is the Quality of the ICC’s Legal Reasoning an Obstacle to Its Ability to Deter International Crimes?
Authors: Kjeldgaard-Pedersen Astrid
Published: August 2020

Given that the Rome Statute is only binding upon its member states, there is a certain element of judicial megalomania in the recurrent claim by the International Criminal Court (ICC) that it acts ‘on behalf of the international community as a whole’ in its endeavour to end impunity for international crimes. Focusing on recent ICC rulings concerning the nature and function of the Court, this article queries whether the quality of the Court’s legal reasoning may have an impact on its long-term deterrence potential. The article suggests that while making self-aggrandizing statements and stretching the boundaries of its legal mandate might, in principle, increase the short-term deterrent effect of the ICC, the Court risks sacrificing a greater good, i.e. its long-term status as a legitimate authority within the field international criminal law. Inconsistent rulings without a solid basis in sound legal analysis may indeed prove to be devastating for the ICC, which is still in the process of establishing itself as a credible institution that commands respect.
Antixenosis, Antibiosis, and Potential Yield Compensatory Response in Barley Cultivars Exposed to Wheat Stem Sawfly (Hymenoptera: Cephidae) Under Field Conditions
Authors: Achhami Buddhi B , Reddy Gadi V P , Sherman Jamie D , Peterson Robert K D , Weaver David K
Published: August 2020

Wheat stem sawfly, Cephus cinctus Norton, is an economically serious pest of cereals grown in North America. Barley cultivars were previously planted as resistant crops in rotations to manage C. cinctus, but due to increasing levels of injury to this crop, this is no longer a valid management tactic in Montana. Therefore, we aimed to understand antixenosis (behavioral preference), antibiosis (mortality), and potential yield compensation (increased productivity in response to stem injuries) in barley exposed to C. cinctus. We examined these traits in eight barley cultivars. Antixenosis was assessed by counting number of eggs per stem and antibiosis was assessed by counting infested stems, dead larvae, and stems cut by mature larvae. Potential yield compensation was evaluated by comparing grain yield from three categories of stem infestation: 1) uninfested, 2) infested with dead larva, and 3) infested cut by mature larva at crop maturity. We found the greatest number of eggs per infested stem (1.80 ± 0.04), the highest proportion of infested stems (0.63 ± 0.01), and the highest proportion of cut stems (0.33 ± 0.01) in ‘Hockett’. Seven out of eight cultivars had greater grain weight for infested stems than for uninfested stems. These cultivars may have compensatory responses to larval feeding injury. Overall, these barley cultivars contain varying levels of antixenosis, antibiosis, and differing levels of yield compensation. Our results provide foundational knowledge on barley traits that will provide a framework to further develop C. cinctus resistant or tolerant barley cultivars.
The effects of PSA kinetics on the outcome of hypofractionated salvage radiotherapy for biochemical recurrence of prostate cancer after prostatectomy
Authors: Ishikawa Hitoshi , Higuchi Keiko , Kaminuma Takuya , Takezawa Yutaka , Saito Yoshitaka , Etsunaga Toru , Maruo Kazushi , Kawamura Hidemasa , Kubo Nobuteru , Nakano Takashi , Kobayashi Mikio
Published: August 2020

The feasibility and efficacy of hypofractionated salvage radiotherapy (HS-RT) for prostate cancer (PC) with biochemical recurrence (BR) after prostatectomy, and the usefulness of prostate-specific antigen (PSA) kinetics as a predictor of BR, were evaluated in 38 patients who received HS-RT without androgen deprivation therapy between May 2009 and January 2017. Their median age, PSA level and PSA doubling time (PSA-DT) at the start of HS-RT were 68 (53–74) years, 0.28 (0.20–0.79) ng/ml and 7.7 (2.3–38.5) months, respectively. A total dose of 60 Gy in 20 fractions (three times a week) was three-dimensionally delivered to the prostate bed. After a median follow-up of 62 (30–100) months, 19 (50%) patients developed a second BR after HS-RT, but only 1 patient died before the last follow-up. The 5-year overall survival and BR-free survival rates were 97.1 and 47.4%, respectively. Late grade 2 gastrointestinal and genitourinary morbidities were observed in 0 and 5 (13%) patients, respectively. The PSA level as well as pathological T-stage and surgical margin status were regarded as significant predictive factors for a second BR by multivariate analysis. BR developed within 6 months after HS-RT in 11 (85%) of 13 patients with a PSA-DT < 10 months compared with 1 (17%) of 6 with a PSA-DT ≥ 10 months (median time to BR: 3 vs 14 months, P < 0.05). Despite the small number of patients, our HS-RT protocol seems feasible, and PSA kinetics may be useful for predicting the risk of BR and determining the appropriate follow-up schedule.
A Survey of Glaucoma Surgery Practice Patterns in the Veterans Health Administration
Authors: Olivieri Daniel J , Lynch Mary G , Cockerham Glenn C , Greenberg Paul B
Published: August 2020

Introduction

Glaucoma surgical practice patterns are not well described in the United States (US). This study aims to evaluate the indications for and potential barriers to glaucoma surgery in the Veterans Health Administration (VHA).

Materials and Methods

An anonymous 10-question survey using REDCap (Nashville, TN) software was sent by mail (with web link) and email to ophthalmology chiefs at the 86 academically affiliated Veterans Affairs Medical Centers (VAMCs). Academic-affiliated VAMCs were selected because of their patient range and role in ophthalmic education. Non-responders received two reminder e-mails and two phone calls; the survey was closed after 6 weeks. The data were analyzed using descriptive statistics.

Results

The response rate was 45% (39/86). Most respondents (92%) worked in an integrated eye clinic with both ophthalmology and optometry services. Almost half of the respondents (49%; 19/39) believed that laser trabeculoplasty (LTP) was an option for initial glaucoma therapy. Noncompliance was a commonly reported indication for LTP (95%), tube shunt procedures (65%), micro-invasive glaucoma surgery (59%), and trabeculectomy (48.7%). One third of the respondents believed that there were delays in glaucoma care. The respondents noted that significant barriers in access to surgery included lack of transportation (69%), scheduling challenges (62%), and delayed referral (62%).

Conclusion

This survey of glaucoma surgery practice patterns highlights the growing role of LTP and suggests that non-compliance and access remain significant barriers to glaucoma surgical care within the VHA.
Single-cell transcriptomic landscape of human blood cells
Authors: Xie Xiaowei , Liu Mengyao , Zhang Yawen , Wang Bingrui , Zhu Caiying , Wang Chenchen , Li Qing , Huo Yingying , Guo Jiaojiao , Xu Changlu , Hu Linping , Pang Aiming , Ma Shihui , Wang Lina , Cao Wenbin , Chen Shulian , Li Qiuling , Zhang Sudong , Zhao Xueying , Zhou Wen , Luo Hongbo , Zheng Guoguang , Jiang Erlie , Feng Sizhou , Chen Lixiang , Shi Lihong , Cheng Hui , Hao Sha , Zhu Ping , Cheng Tao
Published: August 2020

High throughput single-cell RNA-seq has been successfully implemented to dissect the cellular and molecular features underlying hematopoiesis. However, an elaborate and comprehensive transcriptome reference of the whole blood system is lacking. Here, we profiled the transcriptomes of 7551 human blood cells representing 32 immunophenotypic cell types, including hematopoietic stem cells, progenitors and mature blood cells derived from 21 healthy donors. With high sequencing depth and coverage, we constructed a single-cell transcriptional atlas of blood cells (ABC) on the basis of both protein-coding genes and long noncoding RNAs (lncRNAs), and showed a high consistence between them. Notably, putative lncRNAs and transcription factors regulating hematopoietic cell differentiation were identified. While common transcription factor regulatory networks were activated in neutrophils and monocytes, lymphoid cells dramatically changed their regulatory networks during differentiation. Furthermore, we showed a subset of nucleated erythrocytes actively expressing immune signals, suggesting the existence of erythroid precursors with immune functions. Finally, a web portal offering transcriptome browsing and blood cell type prediction has been established. Thus, our work provides a transcriptional map of human blood cells at single-cell resolution, thereby offering a comprehensive reference for the exploration of physiological and pathological hematopoiesis.
An Adherence-Enhancing Program Increases Retention in Care in the Swiss HIV Cohort
Authors: Kamal Susan , Glass Tracy R , Doco-Lecompte Thanh , Locher Sophie , Bugnon Olivier , Parienti Jean-Jacques , Cavassini Matthias , Schneider Marie P
Published: August 2020

Background

This study tested a theory-based adherence-enhancing intervention: the “Interprofessional Medication Adherence Program” (IMAP) to increase human immunodeficiency virus (HIV) retention in care.

Methods

We retrospectively compared our intervention center (intervention group [IG]) with a standard of care center (control group [CG]) both participating in the Swiss HIV Cohort Study between 2004 and 2012. Endpoints were defined as >6-month and >12-month gaps in care for intervals of care longer than 6 and 12 months without any blood draw. Inverse probability of treatment weights was used to adjust for differences between patients at the 2 centers. Viral failure was defined as ribonucleic acid ≥50 copies/mL after 24+ weeks on antiretrovirals.

Results

The IG included 451 patients, CG 311. In the IG, 179 (40%) patients took part in the IMAP for a median of 27 months (interquartile range, 12–45). Gaps in care of ≥6 months were significantly more likely to happen in the CG versus IG (74.6% vs 57%, P < .001). The median time until the first treatment gap was longer in the IG vs CG (120 vs 84 weeks, P < .001). Gaps in care of ≥12 months evaluated in 709 (93%) patients were significantly more likely to occur in the CG compared with the IG (22.6% vs 12.5%, P < .001). The rate of viral failure was significantly lower in the IG (8.3% vs 15.1%, P = .003).

Conclusions

This study, in a real-world setting, shows the effectiveness of the IMAP to reduce 6- and 12-month gaps in follow up among people with HIV. These results should be confirmed by studies in other settings.
Efficacy and Safety of Switching to Dolutegravir With Boosted Darunavir in Virologically Suppressed Adults With HIV-1: A Randomized, Open-Label, Multicenter, Phase 3, Noninferiority Trial: The DUALIS Study
Authors: Spinner Christoph D , Kümmerle Tim , Schneider Jochen , Cordes Christiane , Heiken Hans , Stellbrink Hans-Jürgen , Krznaric Ivanka , Scholten Stephan , Jensen Björn , Wyen Christoph , Viehweger Marin , Lehmann Clara , Sprinzl Martin , Stoehr Albrecht , Bickel Markus , Jessen Heiko , Obst Wilfried , Spornraft-Ragaller Petra , Khaykin Pavel , Wolf Eva , Boesecke Christoph ,   DUALIS Study Group, Spinner Christoph D , Jensen Björn , Lutz Thomas , Spornraft-Ragaller Petra , Stellbrink  , Hower Martin , Bohr Ulrich , Obst Wilfried , Krznaric Ivanka , Sprinzl Martin , Audebert Franz , Kuemmerle Tim , Scholten Stefan , Hillenbrand Heribert , Cordes Christiane , Knechten Heribert , Kuhlmann Birger , Jessen Heiko , Beck Patrick , Fätkenheuer Gerd , Klinker Hartwig H F , Rockstroh Juergen K , Esser Stefan , Stephan Christoph , Degen Olaf , Bellmunt-Zschäpe Andreas , Khaykin Pavel , Brockmeyer Norbert , Stoehr Albrecht
Published: August 2020

Background

Dolutegravir (DTG) and boosted darunavir (bDRV) are potent antiretrovirals with a high resistance barrier and might be valuable switch options for people with HIV (PWH).

Methods

DUALIS, a randomized, open-label, phase 3b, noninferiority clinical trial, compared the switch to DTG + bDRV (2DR) with continuation of 2 nucleoside reverse transcriptase inhibitors (2NRTI) + bDRV (3DR). PWH with HIV RNA <50 copies/mL taking 2NRTI + bDRV (3DR) for ≥24 weeks (1 accepted blip <200 copies/mL) were randomized to either switch to DTG 50 mg + DRV 800 mg (boosted with 100 mg of ritonavir) or continue taking 3DR. The primary end point (PE) was the proportion of HIV RNA <50 copies/mL at week (W) 48. Change in NRTI backbone was not classified as failure. The estimated sample size for PE analysis was 292; the noninferiority margin was ≤–10.0%.

Results

In total, 263 subjects were randomized and treated (2DR n = 131, 3DR n = 132; 90.1% male; 89.7% Caucasian; median age [interquartile range], 48 [39–54] years). At W48, 86.3% (n = 113/131) of the 2DR subject and 87.9% (n = 116/132) of the 3DR subjects had HIV RNA <50 copies/mL; the difference between arms was –1.6% (95.48% CI, based on the adjusted alpha level accounting for the interim analysis at W24, –9.9% to +6.7%; discontinuations due to adverse events: 2DR, 4.6% [n = 6]; 3DR, 0.8% [n = 1]). Kaplan-Meier estimates of confirmed HIV RNA ≥50 copies/mL at W48 were 1.6% (n = 2) in the 2DR and 3.1% (n = 4) in the 3DR group. Development of treatment-emergent resistance was not observed.

Conclusions

Switching to DTG + bDRV was noninferior to continuing 3DR in subjects already treated with bDRV.
FOREST unbiased Galactic plane imaging survey with the Nobeyama 45 m telescope (FUGIN). VIII. Possible evidence of cloud–cloud collisions triggering high-mass star formation in the giant molecular cloud M 16 (Eagle Nebula)
Authors: Nishimura Atsushi , Fujita Shinji , Kohno Mikito , Tsutsumi Daichi , Minamidani Tetsuhiro , Torii Kazufumi , Umemoto Tomofumi , Matsuo Mitsuhiro , Tsuda Yuya , Kuriki Mika , Kuno Nario , Sano Hidetoshi , Yamamoto Hiroaki , Tachihara Kengo , Fukui Yasuo
Published: August 2020

M 16, the Eagle Nebula, is an outstanding H ii region which exhibits extensive high-mass star formation and hosts remarkable “pillars.” We herein obtained new 12COJ = 1–0 data for the region observed with NANTEN2, which were combined with the 12COJ = 1–0 data obtained using the FOREST unbiased galactic plane imaging with Nobeyama 45 m telescope (FUGIN) survey. These observations revealed that a giant molecular cloud (GMC) of ∼1.3 × 105 M⊙ is associated with M 16, which extends for 30 pc perpendicularly to the galactic plane, at a distance of 1.8 kpc. This GMC can be divided into the northern (N) cloud, the eastern (E) filament, the southeastern (SE) cloud, the southeastern (SE) filament, and the southern (S) cloud. We also found two velocity components (blueshifted and redshifted components) in the N cloud. The blueshifted component shows a ring-like structure, and the redshifted one coincides with the intensity depression of the ring-like structure. The position–velocity diagram of the components showed a V-shaped velocity feature. The spatial and velocity structures of the cloud indicated that two different velocity components collided with each other at a relative velocity of 11.6 km s−1. The timescale of the collision was estimated to be ∼4 × 105 yr. The collision event reasonably explains the formation of the O9V star ALS 15348, as well as the shape of the Spitzer bubble N19. A similar velocity structure was found in the SE cloud, which is associated with the O7.5V star HD 168504. In addition, the complementary distributions of the two velocity components found in the entire GMC suggested that the collision event occurred globally. On the basis of the above results, we herein propose a hypothesis that the collision between the two components occurred sequentially over the last several 106 yr and triggered the formation of O-type stars in the NGC 6611 cluster in M 16.
The Cyclicality of Sales and Aggregate Price Flexibility
Authors: Kryvtsov Oleksiy , Vincent Nicolas
Published: August 2020

Macroeconomists traditionally ignore temporary price markdowns (“sales”) under the assumption that they are unrelated to aggregate phenomena. We revisit this view. First, we provide robust evidence from the U.K. and U.S. CPI micro data that the frequency of sales is strongly countercyclical, as much as doubling during the Great Recession. Second, we build a general equilibrium model in which cyclical sales arise endogenously as retailers try to attract bargain hunters. The calibrated model fits well the business cycle co-movement of sales with consumption and hours worked, and the strong substitution between market work and shopping time documented in the time-use literature. The model predicts that after a monetary contraction, the heightened use of discounts by firms amplifies the fall in the aggregate price level, attenuating by a third the one-year response of real consumption.
FIELD ENHANCEMENT AND SIZE OF RADIO-FREQUENCY HOTSPOTS INDUCED BY MAXIMUM RATIO FIELD COMBINING IN FIFTH GENERATION NETWORK
Authors: Velghe Maarten , Shikhantsov Sergei , Tanghe Emmeric , Martens Luc , Joseph Wout , Thielens Arno
Published: August 2020

The goal of this paper is to experimentally assess the field enhancement and hotspot size of radio frequency electromagnetic fields created by the Maximum Ratio Combining (MRC) precoding scheme using lab measurements at 3.5, 5.5 and 11 GHz. MRC is an adaptive precoding scheme used by Massive Multiple Input Multiple Output systems, one of the enabling techniques of the fifth generation of telecommunications (5G). A virtual antenna array was used to compare MRC with two passive precoding schemes: the Random Phase Model (RPM) and the Centerline Beam Model (CBM). The field enhancement going from CBM to MRC was largest in obstructed line of sight (OLOS), ranging from 1.9 to 7.4 dB. The field enhancement going from RPM to MRC was about 9.5 dB across frequency bands in both line of sight (LOS) and OLOS. The hotspot size, quantified by the full width at half maximum (FWHM), ranged from 0.5 wavelengths to one wavelength.
Intraspecific Variability in Root Traits and Edaphic Conditions Influence Soil Microbiomes Across 12 Switchgrass Cultivars
Authors: Ulbrich Tayler C. , Friesen Maren L. , Roley Sarah S. , Tiemann Lisa K. , Evans Sarah E.
Published: August 2020

Microbial communities help plants access nutrients and tolerate stress. Some microbiomes are specific to plant genotypes and, therefore, may contribute to intraspecific differences in plant growth and be a promising target for plant breeding. Switchgrass (Panicum virgatum) is a potential bioenergy crop with broad variation in yields and environmental responses; recent studies suggest that associations with distinct microbiomes may contribute to variation in cultivar yields. We used a common garden experiment to investigate variation in 12 mature switchgrass cultivar soil microbiomes and, furthermore, to examine how root traits and soil conditions influence microbiome structure. We found that average root diameter varied up to 33% among cultivars and that the cultivars also associated with distinct soil microbiomes. Cultivar had a larger effect on the soil bacterial than fungal community but both were strongly influenced by soil properties. Root traits had a weaker effect on microbiome structure but root length contributed to variation in the fungal community. Unlike the soil communities, the root bacterial communities did not group by cultivar, based on a subset of samples. Microbial biomass carbon and nitrogen and the abundance of several dominant bacterial phyla varied between ecotypes but overall the differences in soil microbiomes were greater among cultivars than between ecotypes. Our findings show that there is not one soil microbiome that applies to all switchgrass cultivars, or even to each ecotype. These subtle but significant differences in root traits, microbial biomass, and the abundance of certain soil bacteria could explain differences in cultivar yields and environmental responses.
Colonization of Wild Blackberry Plants in California by Fusarium oxysporum f. sp. mori
Authors: Pastrana Ana M. , Watson Dean C. , Gordon Thomas R.
Published: August 2020

Fusarium oxysporum f. sp. mori, the causal agent of Fusarium wilt of blackberry, was first reported in California and Mexico in 2016. A limited survey of the population revealed this pathogen to be one of the most diverse formae speciales of F. oxysporum. We explored the possibility that strains of F. oxysporum pathogenic to commercial blackberry could also be recovered from wild blackberry (Rubus spp.) in California. For this purpose, wild Rubus species in blackberry nurseries, fruit production fields, and nearby areas were collected between 2017 and 2019. Thirty-four isolates of F. oxysporum were recovered from asymptomatic Rubus armeniacus and Rubus ursinus plants. Based on sequence of the translation elongation factor 1-α, somatic compatibility, and pathogenicity to blackberry, 16 isolates were confirmed as F. oxysporum f. sp. mori. These isolates were associated with three somatic compatibility groups, one of which was first identified in this study. Recovery of the pathogen confirmed that wild blackberry plants can act as a reservoir of inoculum of F. oxysporum f. sp. mori and that it can move from wild blackberry plants to commercial cultivars or vice versa.
Resistance to Quinone Outside Inhibitor Fungicides Conferred by the G143A Mutation in Cercospora sojina (Causal Agent of Frogeye Leaf Spot) Isolates from Michigan, Minnesota, and Nebraska Soybean Fields
Authors: Neves Danilo L. , Chilvers Martin I. , Jackson-Ziems Tamra A. , Malvick Dean K. , Bradley Carl A.
Published: August 2020

Frogeye leaf spot, caused by Cercospora sojina, is an important disease of soybean (Glycine max) in the United States. An important tactic to manage frogeye leaf spot is to apply foliar fungicides. Isolates of C. sojina were collected from soybean fields in one county in Michigan, three counties in Minnesota, and 10 counties in Nebraska in 2019, and they were tested for resistance to quinone outside inhibitor (QoI) fungicides using a discriminatory dose assay, a PCR assay, and DNA sequencing. Results of the testing indicated that QoI fungicide-resistant isolates were detected in isolates from all counties. Testing results also indicated that the G143A mutation was responsible for the QoI fungicide resistance. This is the first report of QoI fungicide-resistant C. sojina isolates in Michigan, Minnesota, and Nebraska and expands the geographical distribution of QoI fungicide-resistant C. sojina isolates to 18 states in total.
Principles Guiding Nonpandemic Critical Care Research During a Pandemic
Authors: Cook Deborah J. , Kho Michelle E. , Duan Eric H. , Alhazzani Waleed , Takaoka Alyson , Clarke France J. , Zytaruk Nicole , Vanstone Meredith
Published: August 2020

Objectives:

To describe the importance of critical care clinical research that is not pandemic-focused during pandemic times; outline principles to assist in the prioritization of nonpandemic research during pandemic times; and propose a guiding framework for decisions about whether, when and how to continue nonpandemic research while still honoring the moral and scientific imperative to launch research that is pandemic-focused.

Design/Data Sources:

Using in-person, email, and videoconference exchanges, we convened an interprofessional clinical research group, conducted a literature review of empirical studies, ethics documents and expert commentaries (2010 to present), and viewed traditional and social media posts (March 2020 to May 2020). Stakeholder consultation involved scientific, ethics, clinical, and administrative leaders.

Setting:

Clinical research in the ICU.

Patients:

Patients with and without coronavirus disease 2019.

Interventions:

None.

Measurements and Main Results:

While clinical research should be prioritized to advantage patients with coronavirus disease 2019 in order to care for affected patients, it ideally would not unduly disadvantage patients without coronavirus disease 2019. Thus, timely, rigorous, relevant, and ethical clinical research is needed to improve the care and optimize outcomes for both patients with and without coronavirus disease 2019, acknowledging how many studies that are not exclusively focused on coronavirus disease 2019 remain relevant to patients with coronavirus disease 2019. Considerations to continue nonpandemic-focused research include the status of the pandemic, local jurisdictional guidance, capacity and safety of bedside and research personnel, disposition of patients already enrolled in nonpandemic studies, analyzing characteristics of each nonpandemic-focused study, research oversight, and final reporting requirements.

Conclusions:

Deliberation about continuing nonpandemic research should use objective, transparent criteria considering several aspects of the research process such as bedside and research staff safety, infection control, the informed consent model, protocol complexity, data collection, and implementation integrity. Decisions to pause or pursue nonpandemic research should be proportionate, transparent, and revisited as the pandemic abates.
Clear Cell Hidradenoma—Basal Cell Carcinoma Collision
Authors: Piqué-Duran Enric , Duran-Hernández MªCristina , Pérez-Cejudo Juan A. , García-Vázquez Odalys
Published: August 2020

A 91-year-old man presented with a tumor on the left temporal area, clinically suspicious of basal cell carcinoma. The histopathologic study showed a central solid-cystic tumor composed by 3 different types of cells (clear or finely granular cells, polygonal cells, and squamoid cells). It had a sclerotic stroma. At the periphery, another tumor composed by smaller interconnected nests was evident. Some nests were separated from the stroma by clefts. The stroma of this second tumor was highly cellular. There was a sharp delimitation between both tumors, with no transitional area. Immunochemistry demonstrated they are different tumor. A diagnosis of clear cell hidradenoma–basal cell carcinoma collision was performed. To the best of our knowledge, this is the first description of this challenging association.