bluuebunny/crossref_metadata_2025 huggingface dataset:
Alterations in regulatory T cells and immune checkpoint molecules in pancreatic cancer patients receiving FOLFIRINOX or gemcitabine plus nab-paclitaxel
Authors: Sams L. , Kruger S. , Heinemann V. , Bararia D. , Haebe S. , Alig S. , Haas M. , Zhang D. , Westphalen C. B. , Ormanns S. , Metzger P. , Werner J. , Weigert O. , von Bergwelt-Baildon M. , Rataj F. , Kobold S. , Boeck S.
Published: April 2021

Purpose

This pilot study aimed on generating insight on alterations in circulating immune cells during the use of FOLFIRINOX and gemcitabine/nab-paclitaxel in pancreatic ductal adenocarcinoma (PDAC).

Patients and methods

Peripheral blood mononuclear cells were isolated before and 30 days after initiation of chemotherapy from 20 patients with advanced PDAC. Regulatory T cells (FoxP3+) and immune checkpoints (PD-1 and TIM-3) were analyzed by flow cytometry and immunological changes were correlated with clinical outcome.

Results

Heterogeneous changes during chemotherapy were observed in circulating T-cell subpopulations with a pronounced effect on PD-1+ CD4+/CD8+ T cells. An increase in FoxP3+ or PD-1+ T cells had no significant effect on survival. An increase in TIM3+/CD8+ (but not TIM3+/CD4+) T cells was associated with a significant inferior outcome: median progression-free survival in the subgroup with an increase of TIM-3+/CD8+ T cells was 6.0 compared to 14.0 months in patients with a decrease/no change (p = 0.026); corresponding median overall survival was 13.0 and 20.0 months (p = 0.011), respectively.

Conclusions

Chemotherapy with FOLFIRNOX or gemcitabine/nab-paclitaxel induces variable changes in circulating T-cell populations that may provide prognostic information in PDAC.
Extended single-dose toxicity study of [211At]NaAt in mice for the first-in-human clinical trial of targeted alpha therapy for differentiated thyroid cancer
Authors: Watabe Tadashi , Kaneda-Nakashima Kazuko , Ooe Kazuhiro , Liu Yuwei , Kurimoto Kenta , Murai Takashi , Shidahara Yuka , Okuma Kenji , Takeuchi Masanori , Nishide Masayuki , Toyoshima Atsushi , Shinohara Atsushi , Shirakami Yoshifumi
Published: April 2021

Objective

Astatine (211At) is a promising alpha emitter as an alternative to iodine (131I). We are preparing the first-in-human (FIH) clinical trial of targeted alpha therapy for differentiated thyroid cancer in consultation with Pharmaceuticals and Medical Devices Agency. Here, we performed an extended single-dose toxicity examination under a reliability standard, as a preclinical safety assessment of [211At]NaAt to determine the FIH dose.

Methods

[211At]NaAt solution was injected into normal 6-week-old mice (male (n = 50) and female (n = 50), body weight: male 33.2 ± 1.7 g, female 27.3 ± 1.5 g), which were then divided into four groups: 5 MBq/kg (n = 20), 20 MBq/kg (n = 20), 50 MBq/kg (n = 30), saline control (n = 30). The mice were followed up for 5 days (primary evaluation point for acute toxicity: n = 80) or 14 days (n = 20: evaluation point for recovery) to monitor general condition and body weight change. At the end of the observation period, necropsy, blood test, organ weight measurement, and histopathological examination were performed. For body weight, blood test, and organ weight, statistical analyses were performed to compare data between the control and injected groups.

Results

No abnormal findings were observed in the general condition of mice. In the 50 MBq/kg group, males (days 3 and 5) showed a significant decrease in body weight compared with the control. However, necropsy did not differ significantly beyond the range of spontaneous lesions. In the blood test, males (50 MBq/kg) and females (50 MBq/kg) showed a decrease in white blood cell and platelet counts on day 5, and recovery on day 14. In the testis, a considerable weight decrease was observed on day 14 (50 MBq/kg), and multinucleated giant cells were observed in all mice, indicating a significant change related to the administration of [211At]NaAt.

Conclusions

In the extended single-dose toxicity study of [211At]NaAt, administration of high doses resulted in weight loss, transient bone marrow suppression, and pathological changes in the testis, which require consideration in the FIH clinical trial.
Hierarchy and the size of a firm
Authors: Hiller Tobias
Published: April 2021

In this note, we apply weighted hierarchical games of cooperative game theory to the problem of optimal firm size of the firm. In particular, we analyze the influence of production technology on the size of the firm. Our note enhances previous approaches using a permission structure with equally strong relationships between predecessor and direct successors.
Exposure to Arsenic in the Air and 15-F2t-Isoprostane in Urine in a Sub-population of Inhabitants of a Copper Smelter Region
Authors: Skoczynska Anna , Skoczynska Marta , Turczyn Barbara , Wojakowska Anna , Gruszczynski Leszek , Scieszka Marek
Published: April 2021

Most studies on arsenic toxicity have been conducted among populations exposed to arsenic contained in drinking water. Relatively little research concerns effects of airborne arsenic. The aim of this study was to determine whether there is an association between urinary 15-F2t-isoprostane (u15-F2t-IsoP) levels in relation to renal function (urinary creatinine and N-acetyl-β-d-glucosaminidase––uNAG) and urinary arsenic (uAs) in inhabitants from copper smelter impact zone. The secondary purpose of the analysis was to assess utility of a potential association between uAs and u15-F2t-IsoP as a biomarker of systemic oxidative stress. Urinary 15-F2t-IsoP, NAG, and creatinine were measured in 967 urine samples collected from 649 adult women (51.9 ± 13.2 years old) and 318 adult men (53.8 ± 14.9 years old). Total uAs concentration was measured in 918 samples using HPLC-ICP-MS. Arsenic species, such as inorganic arsenic, methylarsonic acid, dimethylarsinic acid, and arsenobetaine, were measured in urine collected from 255 participants with uAs exceeding the upper norm. Data were analyzed using multivariate linear regression and logistic regression models. In the studied population urinary creatinine was positively associated with uAs. A positive linear correlation (p < 0.0000) between lg(uAs) and u15-F2t-IsoP was found both for normal and elevated uAs. A positive linear correlation was observed also between lg(ΣuAs) and u15-F2t-IsoP (p < 0.0000). In the logistic regression model, after adjustment for confounders, elevated uAs was the only predictor of increased u15-F2t-IsoP (OR = 1.31, 95% CI 1.08–1.59,p < 0.01). Cigarette smoking was associated with renal proximal tubular dysfunction only in people with uNAG concentration above 75th quartile. In the studied population chronically exposed to airborne arsenic, increase in urinary arsenic is associated with renal dysfunction and systemic oxidative stress. Urinary 15-F2t-isoprostane may be useful in the monitoring of health status in populations exposed to airborne arsenic.
Smart Roads Geometric Design Criteria and Capacity Estimation Based on AV and CAV Emerging Technologies. A Case Study in the Trans-European Transport Network
Authors: Guerrieri Marco
Published: April 2021

Smart roads, AV and CAV are emerging technologies that represent the new paradigm of mobility. To support the public and private road operators better prepare themselves to implement these technologies in their respective existing or planned infrastructures, there is an urgent need to develop an integrated analysis framework to evaluate the impact of these novel systems on road capacity and safety in function of different market penetration levels of AVs and CAVs. The research focuses on novel smart road geometric design and review criteria based on the performance of AVs and CAVs. The case study of one of the first planned smart roads in Italy has been analysed.
Evaluation of the performance of titanium and zirconium salts as coagulants in industrial wastewater treatment: pollutant removal, sludge production, and sludge characteristics
Authors: Uysal Ayla , Boyacioglu Eda
Published: April 2021

In this study, titanium tetrachloride (TiCl4), zirconium tetrachloride (ZrCl4), and zirconium oxychloride (ZrOCl2·8H2O) were evaluated using jar test experiments as coagulants and compared with traditional aluminum sulfate (Al2(SO4)3·18H2O) and ferric chloride (FeCl3) for industrial wastewater treatment. The effects of the initial pH of 4–10 and initial coagulant doses of 10–100 mg/L on chemical oxygen demand (COD) and total suspended solids (TSS) removal were investigated. The performances of the five coagulants were also assessed in terms of the settled sludge volume, the sludge volume index (SVI), and removal efficiencies of metals, color, and total phosphorus (TP) under optimum conditions. In addition, the contents of the residual sludge produced for all five tested coagulants under optimum conditions were determined. The results showed that the maximum removal efficiency of COD (69.33%) was achieved using 100 mg/L TiCl4 at pH 8. The maximum removal efficiency of TSS (98.32%) was achieved using 50 mg/L Al2(SO4)3·18H2O at both pH 8 and 10. The settled sludge volume and SVI generated by TiCl4 were lower than that for the other four tested coagulants. ZrCl4, ZrOCl2·8H2O, FeCl3, and Al2(SO4)3·18H2O resulted in 128.13, 92.39, 72.26, and 69.66 mL/g SVI, while that using TiCl4 was 48.84 mL/g. Ti- and Zr-based coagulants achieved better removal efficiencies of TP, Zn, and Cu than FeCl3 and Al(SO4)3·18H2O. The residual sludge from using Ti and Zr coagulants had a very high TP content. The results indicated that Ti- and Zr-based coagulants could be used as alternatives to traditional coagulants for industrial wastewater treatment.
Sarm1-mediated neurodegeneration within the enteric nervous system protects against local inflammation of the colon
Authors: Sun Yue , Wang Qi , Wang Yi , Ren Wenran , Cao Ying , Li Jiali , Zhou Xin , Fu Wei , Yang Jing
Published: April 2021

Axonal degeneration is one of the key features of neurodegenerative disorders. In the canonical view, axonal degeneration destructs neural connections and promotes detrimental disease defects. Here, we assessed the enteric nervous system (ENS) of the mouse, non-human primate, and human by advanced 3D imaging. We observed the profound neurodegeneration of catecholaminergic axons in human colons with ulcerative colitis, and similarly, in mouse colons during acute dextran sulfate sodium-induced colitis. However, we unexpectedly revealed that blockage of such axonal degeneration by the Sarm1 deletion in mice exacerbated the colitis condition. In contrast, pharmacologic ablation or chemogenetic inhibition of catecholaminergic axons suppressed the colon inflammation. We further showed that the catecholaminergic neurotransmitter norepinephrine exerted a pro-inflammatory function by enhancing the expression of IL-17 cytokines. Together, this study demonstrated that Sarm1-mediated neurodegeneration within the ENS mitigated local inflammation of the colon, uncovering a previously-unrecognized beneficial role of axonal degeneration in this disease context.
Stable Lithium-Carbon Composite Enabled by Dual-Salt Additives
Authors: Zheng Lei , Guo Feng , Kang Tuo , Fan Yingzhu , Gu Wei , Mao Yayun , Liu Ya , Huang Rong , Li Zhiyun , Shen Yanbin , Lu Wei , Chen Liwei
Published: April 2021

Lithium metal is regarded as the ultimate negative electrode material for secondary batteries due to its high energy density. However, it suffers from poor cycling stability because of its high reactivity with liquid electrolytes. Therefore, continuous efforts have been put into improving the cycling Coulombic efficiency (CE) to extend the lifespan of the lithium metal negative electrode. Herein, we report that using dual-salt additives of LiPF6 and LiNO3 in an ether solvent-based electrolyte can significantly improve the cycling stability and rate capability of a Li-carbon (Li-CNT) composite. As a result, an average cycling CE as high as 99.30% was obtained for the Li-CNT at a current density of 2.5 mA cm–2 and an negative electrode to positive electrode capacity (N/P) ratio of 2. The cycling stability and rate capability enhancement of the Li-CNT negative electrode could be attributed to the formation of a better solid electrolyte interphase layer that contains both inorganic components and organic polyether. The former component mainly originates from the decomposition of the LiNO3 additive, while the latter comes from the LiPF6-induced ring-opening polymerization of the ether solvent. This novel surface chemistry significantly improves the CE of Li negative electrode, revealing its importance for the practical application of lithium metal batteries.
An inverse Jacobian algorithm for Picard curves
Authors: Lario Joan-C. , Somoza Anna , Vincent Christelle
Published: April 2021

We study the inverse Jacobian problem for the case of Picard curves over$${\mathbb {C}}$$C. More precisely, we elaborate on an algorithm that, given a small period matrix$$\varOmega \in {\mathbb {C}}^{3\times 3}$$Ω∈C3×3corresponding to a principally polarized abelian threefold equipped with an automorphism of order 3, returns a Legendre–Rosenhain equation for a Picard curve with Jacobian isomorphic to the given abelian variety. Our method corrects a formula obtained by Koike–Weng (Math Comput 74(249):499–518, 2005) which is based on a theorem of Siegel. As a result, we apply the algorithm to obtain equations of all the isomorphism classes of Picard curves with maximal complex multiplication by the maximal order of the sextic CM-fields with class number at most$$4$$4. In particular, we obtain the complete list of maximal CM Picard curves defined over$${\mathbb {Q}}$$Q. In the appendix, Vincent gives a correction to the generalization of Takase’s formula for the inverse Jacobian problem for hyperelliptic curves given in [Balakrishnan–Ionica–Lauter–Vincent, LMS J. Comput. Math., 19(suppl. A):283-300, 2016].
Effective estimation algorithm for parameters of multivariate Farlie–Gumbel–Morgenstern copula
Authors: Ota Shuhei , Kimura Mitsuhiro
Published: April 2021

This paper focuses on the parameter estimation for the d-variate Farlie–Gumbel–Morgenstern (FGM) copula ($$d\ge 2$$

d
≥
2

), which has $$2^d-d-1$$

2
d

-
d
-
1

dependence parameters to be estimated; therefore, maximum likelihood estimation is not practical for a large d from the viewpoint of computational complexity. Besides, the restriction for the FGM copula’s parameters becomes increasingly complex as d becomes large, which makes parameter estimation difficult. We propose an effective estimation algorithm for the d-variate FGM copula by using the method of inference functions for margins under the restriction of the parameters. We then discuss its asymptotic normality as well as its performance determined through simulation studies. The proposed method is also applied to real data analysis of bearing reliability.
The Treaty on the Prohibition of Nuclear Weapons
Authors: Black-Branch Jonathan L.
Published: April 2021

The Treaty on the Prohibition of Nuclear Weapons (2017) sets out to challenge deterrence policies and military defence doctrines, taking a humanitarian approach intended to disrupt the nuclear status quo. States with nuclear weapons oppose its very existence, neither participating in its development nor adopting its final text. Civil society groups seem determined, however, to stigmatize and delegitimize nuclear weapons towards their abolition. This book analyzes how the Treaty influences the international security architecture, examining legal, institutional and diplomatic implications of the Treaty and exploring its real and potential impact for both states acceding to the Treaty and those opposing it. It concludes with practical recommendations for international lawyers and policymakers regarding non-proliferation and disarmament matters, ultimately noting that nuclear weapons threaten peace, and everyone should have the right to nuclear peace and freedom from nuclear fear.
A Death Retold in Truth and Rumour
Authors: Musila Grace A.
Published: April 2021

Julie Ann Ward was a British tourist and wildlife photographer who went missing in Kenya's Maasai Mara Game Reserve in 1988 and was eventually found to have been murdered. Her death and the protracted search for her killers, still at large, were hotly contested in the media. Many theories emerged as to how and why she died, generating three trials, several 'true crime' books, and much speculation and rumour. At the core of Grace Musila's study are the following questions: why would this young woman's death be the subject of such strong contestations of ideas and multiple truths? And what does this reveal about cultural productions of truth and knowledge in Kenya and Britain, particularly in the light of the responses to her disappearance of the Kenyan police, the British Foreign Office, and the British High Commission in Nairobi. Building on existing scholarship on African history, narrative, gender and postcolonial studies, the author reveals how the Julie Ward murder and its attendant discourses offer insights into the journeys of ideas, and how these traverse the porous boundaries of the relationship between Kenya and Britain, and, by extension, Africa and the Global North. Grace Musila is a lecturer in the English Department of Stellenbosch University, South Africa
Burnout and Sources of Stress Among Health Care Risk Managers and Patient Safety Personnel During the COVID-19 Pandemic: A Pilot Study
Authors: Card Alan J.
Published: April 2021

Objective:

This study investigates burnout and sources of stress related to the coronavirus disease 2019 (COVID-19) pandemic among a group of health care risk managers/patient safety practitioners.

Methods:

An online survey was used, including the Oldenburg Burnout Inventory (OLBI) and 1 open-ended question: Since the start of the COVID-19 pandemic, what work or non-work-related issues have been causing you the most stress?

Results:

A total of 31 participants completed the OLBI; 27 answered the open-ended question. Over 70% of participants qualified as burned out. A thematic analysis was used to analyze stressors. Key themes included impacts of social distancing, changing duties and workload, real and potential impacts of the virus (eg, fear of infection for self or others), and financial concerns (personal and organizational). Less common themes included untrustworthy and constantly changing guidance, feeling abused by persons in power, and positive comments about the experience of working during the pandemic.

Conclusion:

Burnout and pandemic-related stress may be very common in the health care risk management and patient safety workforce. Additional research is required to more robustly estimate the prevalence of burnout in this population. Meanwhile, the sources of stress identified here may aid health care organizations in taking immediate action to protect this vital workforce.
Addressing Pediatric Mental Health During COVID-19 and Other Disasters: A National Tabletop Exercise
Authors: Gupta Saloni , Schreiber Merritt , McGuire Tona , Newton Christopher
Published: April 2021

Objective:

In the wake of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, rapid identification of pediatric mental health risk is extremely important. The Western Regional Alliance for Pediatric Emergency Management held an integrated, interdisciplinary national tabletop exercise to familiarize mental health and non-mental health professionals with Psychological Simple Triage and Rapid Treatment (PsySTART), an evidence-based triage and incident management system used to evaluate new mental health risk impacts following exposure to traumatic events, such as coronavirus disease (COVID-19).

Methods:

Participants Participants were exposed to 3 practice cases that reflected a combination of “all hazards” scenarios and were asked to triage each case using PsySTART. Participants were asked to interpret results at both an individual site and aggregate county and/or state level.

Results:

The exercise had a total of 115 participants with a total of 156 discrete triage encounters. A user-defined operating picture was created with graphs of aggregate mental health risk data, generating cross-regional, real-time situational awareness. After the exercise, a vast majority of the participants reported confidence in their ability to use PsySTART in their practices.

Conclusions:

Participants are now better equipped with tools to perform mental health triage for early intervention during COVID-19 and other disasters and understand risk on a population level.
Searching for a middle ground? A spectrum of views of causality in qualitative research
Authors: Ruffa Chiara , Evangelista Matthew
Published: April 2021

Qualitative scholars exhibit a wide range of views on and approaches to causality. While some approaches reject causality from the outset, a large strand of qualitative research in political science and international relations does, however, pursue causal explanation. Qualitative scholars nevertheless disagree about what causality means. Our paper reviews what causality means within different strands of qualitative research and how qualitative scholars engage in causal explanations. We focus particular attention on the fertile middle ground between qualitative research that seeks to mimic the statistical model and research that rejects causality entirely. In broad strokes, we understand views of causality as lying on a spectrum and partly overlapping. Along the spectrum, we identify three main clusters: ‘positivist leaning,’ ‘postpositivist leaning,’ and ‘interpretivist leaning.’ Within each cluster, we identify the main traits and provide illustrative examples. We find merit in each of these three clusters of approaches and in the ongoing dialogue among qualitative scholars of different orientations. Understanding similarities and differences in the way various scholars address causality might encourage some to take steps along the spectrum and expand their repertoires to embrace elements of other approaches. By making these distinctions more explicit, we hope to be able to enhance our understanding of different views of causality and the extent to which they overlap and provide the potential for collaboration.
Poor adherence to the Mediterranean diet is associated with increased likelihood of metabolic syndrome components in children: the Healthy Growth Study
Authors: George Elena S , Gavrili Stavroula , Itsiopoulos Catherine , Manios Yannis , Moschonis George
Published: April 2021

Objective:

To examine the associations between the level of adherence to the Mediterranean diet (MedDiet) with obesity, insulin resistance (IR), metabolic syndrome (MetS) and its components in schoolchildren.

Design:

The Healthy Growth Study was a large epidemiological cross-sectional study.

Setting:

School children who were enrolled in primary schools in four counties covering the northern, southern, western and central part of Greece were invited to participate.

Participants:

The study was conducted with a representative sample of 9–13-year-old schoolchildren (n 1972) with complete data. This study applied the KIDMed score to determine ‘poor’ (≤3), ‘medium’ (4-7) and ‘high’ (≥8) adherence of children to the MedDiet. The research hypothesis was examined using multivariate logistic regression models, controlling for potential confounders.

Results:

The percentage of children with ‘poor’, ‘medium’ and ‘high’ adherence to the MedDiet was 64·8 %, 34·2 % and 1 %, respectively. Furthermore, the prevalence of obesity, IR and MetS was 11·6 %, 28·8 % and 3·4 %, respectively. Logistic regression analyses revealed that ‘poor’ adherence to the MedDiet was associated with an increased likelihood for central obesity (OR 1·31; 95 % CI 1·01, 1·73), hypertriglyceridaemia (OR 2·80; 95 % CI 1·05, 7·46) and IR (OR 1·31; 95 % CI 1·05, 1·64), even after adjusting for several potential confounders.

Conclusions:

The present study showed that approximately two-thirds of the examined sample of schoolchildren in Greece have ‘poor’ adherence to the MedDiet, which also increases the likelihood for central obesity, hypertriglyceridaemia and IR. Prospective studies are needed to confirm whether these are cause–effect associations.
What stops us from eating: a qualitative investigation of dietary barriers during pregnancy in Punjab, Pakistan
Authors: Asim Muhammad , Ahmed Zarak H , Nichols Amy R , Rickman Rachel , Neiterman Elena , Mahmood Anita , Widen Elizabeth M
Published: April 2021

Objective:

Adequate dietary intake during pregnancy is vital for the health and nutritional status of both mother and fetus. The nutritional status of reproductive age women in Pakistan is poor, with 14 % being underweight (BMI < 18·5) and 42 % experiencing Fe deficiency anaemia. This may stem from beliefs, practices and other barriers influencing dietary intake. This qualitative study seeks to determine which factors impact dietary intake during pregnancy in rural Punjab.

Design:

In-depth interviews and focus group discussions were conducted and then analysed using thematic analysis.

Setting:

Three purposively selected rural districts (Sahiwal, Okara and Pakpatan) with the highest prevalence of maternal and child malnutrition in the province of Punjab, Pakistan

Participants:

Mothers with children under age two (n 29) and healthcare providers with at least 5 years of experience working in the district (n 12).

Results:

We identified a combination of physiological, socio-cultural and structural barriers that inhibited healthful dietary intake during pregnancy. The primary physiological barriers to optimal dietary intake and dietary practices included food aversions and food cravings. Food classification, fear of a difficult childbirth, fear of high blood pressure and household food politics were the principal socio-cultural barriers. Additionally, two structural barriers, inadequate antenatal counseling and a lack of affordable food options, were identified.

Conclusions:

Our study demonstrates that complex barriers prevent pregnant women in the Punjab area from consuming adequate dietary intake and that antenatal health education programmes and structural interventions are needed to support healthful dietary practices during this critical period.
Potential of a Gravity‐Driven Film Flow Model to Predict Infiltration in a Catchment for Diverse Soil and Land Cover Combinations
Authors: Demand D. , Weiler M.
Published: April 2021

Applying physically based models that include preferential flow (PF) is still very challenging at the catchment scale. A gravity‐driven film flow approach could be a promising concept for modeling PF as it only requires a small number of parameters. We tested if this approach can be used for different soils and land covers within a 247 km2 catchment and if we can find generalizable relationships of the film flow parameters to site or rainfall properties. We used a unique data set from a soil moisture sensor network with 135 instrumented soil profiles in three different geologies (slate, marl, and sandstone) and two land covers (forest and grassland) and fitted the film flow model to around 1,700 infiltration events. The results demonstrate that the physical relationship of film flow was capable to predict wetting front velocity (v) and flow parameters from rainfall input (qs) alone. This relationship was pronounced in grassland sites but weaker for forest sites, probably due to heterogeneity of the rainfall input underneath the canopy. Incorporating the water content into the v‐qs relationship did not improve the quality, but showed that for the film flow the rainfall input and hence gravity is in fact the dominant driver and not capillarity. Furthermore, abstraction of water into the soil matrix during film flow is an important process to be included into the framework with reasonable agreements for marl and sandstone using a multiple linear regression. Film flow and corresponding functional parameter relationships for other regions could improve catchment wide PF modeling in the future.
Fates and Use Efficiency of Nitrogen Fertilizer in Maize Cropping Systems and Their Responses to Technologies and Management Practices: A Global Analysis on Field 15N Tracer Studies
Authors: Quan Zhi , Zhang Xin , Davidson Eric A. , Zhu Feifei , Li Shanlong , Zhao Xinghan , Chen Xin , Zhang Li‐Mei , He Ji‐Zheng , Wei Wenxue , Fang Yunting
Published: April 2021

Nitrogen (N) fertilization has boosted grain production during the past century, while excess N fertilization with declining N use efficiency (NUE) has led to severe pollution in many regions. To achieve the goal of sustainable food production, Technologies and Management Practices (TMPs, e.g., optimum N application rate and methods, N‐transformation inhibitors) have been developed to improve crop yield and NUE and to reduce N losses. However, it remains unclear how N fate has been changed by environmental factors and TMPs. Here, we compiled a dataset of 366 field 15N tracer observations from 74 publications worldwide and conducted a meta‐analysis to examine how environmental conditions and management practices influence the fertilizer‐N fate one growing season after the fertilization of maize. We show that the proportion of 15N taken up by aboveground biomass (NUE15N), was significantly lower in China (33%) than that in North America (42%) and the European Union (54%). Soil organic carbon was the most critical environmental factor positively correlated with NUE15N. Among the nine selected categories of TMPs, deep placement of fertilizer and split application increased the grain yield and decreased the fertilizer‐N loss consistently among studies. Reducing the fertilizer‐N rate could increase the NUE15N but presents risks of yield reduction in some regions. This study demonstrates the importance of SOC and varying impacts of TMPs on the efficiency of fertilizer use in cropping systems globally and provides critical information for farmers and policymakers to improve N management for higher productivity and less pollution.
Health Impact Assessment of the 2020 Washington State Wildfire Smoke Episode: Excess Health Burden Attributable to Increased PM2.5 Exposures and Potential Exposure Reductions
Authors: Liu Yisi , Austin Elena , Xiang Jianbang , Gould Tim , Larson Tim , Seto Edmund
Published: April 2021

Major wildfires starting in the summer of 2020 along the west coast of the United States made PM2.5 concentrations in this region rank among the highest in the world. Washington was impacted both by active wildfires in the state and aged wood smoke transported from fires in Oregon and California. This study aims to estimate the magnitude and disproportionate spatial impacts of increased PM2.5 concentrations attributable to these wildfires on population health. Daily PM2.5 concentrations for each county before and during the 2020 Washington wildfire episode (September 7–19) were obtained from regulatory air monitors. Utilizing previously established concentration‐response function (CRF) of PM2.5 (CRF of total PM2.5) and odds ratio (OR) of wildfire smoke days (OR of wildfire smoke days) for mortality, we estimated excess mortality attributable to the increased PM2.5 concentrations in Washington. On average, daily PM2.5 concentrations increased 97.1 μg/m3 during the wildfire smoke episode. With CRF of total PM2.5, the 13‐day exposure to wildfire smoke was estimated to lead to 92.2 (95% CI: 0.0, 178.7) more all‐cause mortality cases; with OR of wildfire smoke days, 38.4 (95% CI: 0.0, 93.3) increased all‐cause mortality cases and 15.1 (95% CI: 0.0, 27.9) increased respiratory mortality cases were attributable to the wildfire smoke episode. The potential impact of avoiding elevated PM2.5 exposures during wildfire events significantly reduced the mortality burden. Because wildfire smoke episodes are likely to impact the Pacific Northwest in future years, continued preparedness and mitigations to reduce exposures to wildfire smoke are necessary to avoid excess health burden.
Using Large Ensembles to Identify Regions of Systematic Biases in Moderate‐to‐Heavy Daily Precipitation
Authors: Goldenson N. , Thackeray C. W. , Hall A. D. , Swain D. L. , Berg N.
Published: April 2021

Because of internal variability in both the real‐world and global climate models, it is unclear whether disagreement between models and observations reflects true systematic differences, or different phasing of internal variability in the short observational period. Here, we address this issue through an examination of moderate‐to‐heavy precipitation in large ensembles of global climate models. We find that model inconsistency with a global observational product is lowest for extratropical precipitation in northern hemisphere winter. The inconsistency is systematically greater for the southern hemisphere winter, but the difference between hemispheres could be due to observational quality. Moderate‐to‐heavy extratropical winter precipitation is less inconsistent than moderate‐to‐heavy tropical precipitation in most models. Within the tropics, moderate‐to‐heavy precipitation is particularly inconsistent with the reference in regions including the Caribbean (especially during JJA), the northern and southern flanks of the Pacific and Atlantic ITCZ, and the Indian Ocean.
Revealing the Morning Transition in the Mountain Boundary Layer Using Fiber‐Optic Distributed Temperature Sensing
Authors: Fritz A. M. , Lapo K. , Freundorfer A. , Linhardt T. , Thomas C. K.
Published: April 2021

In the morning, the nocturnal stable boundary layer, SBL, transitions into its daytime convective counterpart substantially impacting the distribution of temperature, humidity, and pollutants. Applying distributed temperature sensing (DTS) below a tethered balloon (2–200 m) and along a tower (0–11 m), for the first time we observed three morning transitions (MTs) in a mountain boundary layer with high temporal (<10 s) and spatial (<0.25 m) resolutions. We show that MTs are best derived from a change in static stability from synchronous DTS observations. Our findings confirm that the MT occurs at the SBL top and bottom simultaneously, and identify horizontal heat advection as a main driver aiding solar surface heating in this midrange mountain valley. We conclude that heterogenous land use and mountainous topography cause complex interactions between valley‐scale and local airflows leading to thermal signatures characterized by strong, small‐scale variability. Our study highlights DTS as a crucial tool for investigating complex thermodynamic processes.
The Relative Importance of Geomagnetic Storm Signatures on the Total Electron Content Perturbations Over the Continental US
Authors: Debchoudhury Shantanab , Sardana Disha , Earle Gregory D.
Published: April 2021

A study of 37 large solar storms occurring in the equinox periods from 2000 to 2018 is presented to quantify their effects on total electron content (TEC) variations in the ionosphere over the North American sector. The dependence of storm‐related TEC enhancements and depletions is studied as a function of various storm parameters using machine‐learning and statistical algorithms to quantify their relative importance. The variables under consideration include the onset time and duration of each storm, as well as characteristic scalar values derived from ring current variations detected by a network of ground‐based magnetometers. The TEC data used in the study are taken from the Continuously Operating Reference Station network of ground‐based GPS measurements, archived in the Madrigal database. The agreement and disagreement of the results across the different methods studied, along with the relative uncertainties in model prediction capability of the machine‐learning study, show that the geo‐effectiveness of large storms in the equinox periods is more closely related to the storm onset time and to ionospheric preconditioning than to any other parameters used in characterizing the storm. The effects in the higher latitude regions are shown to be very different from the lower latitude regions over the North American sector. This behavior can possibly be explained through storm‐induced changes in the atmospheric chemistry and the related temperature‐dependent production and loss processes at the higher latitudes.
Linking Deep and Shallow Convective Mass Fluxes via an Assumed Entrainment Distribution in CAM5‐CLUBB: Parameterization and Simulated Precipitation Variability
Authors: Yang Ben , Wang Minghuai , Zhang Guang J. , Guo Zhun , Huang Anning , Zhang Yaocun , Qian Yun
Published: April 2021

We modify the Zhang‐McFarlane (ZM) deep convection scheme in the Community Atmosphere Model version 5 to couple it with a unified parameterization for boundary‐layer turbulence and shallow convection, that is, Cloud Layers Unified by Binormals (CLUBB). By assuming a lognormal distribution of entrainment rate across the entire moist convective regimes, we link mass fluxes between shallow and deep convection, which are partitioned by the entrainment rate of the shallowest deep convective plume. Hence, a new deep convective closure is established which is coupled to the sub‐grid vertical motion variability in CLUBB. The convection feedback (or memory) effects are also considered to decrease the entrainment spectrum width and enhance the vertical velocity variability that further affect deep convection. Results show that the revised scheme improves the precipitation simulations in terms of the mean state and variability at various timescales, such as the alleviated double‐intertropical convergence zone and more realistic simulations of the seasonal variation of monsoon precipitation over East Asia, Madden‐Julian Oscillation, and precipitation diurnal phase propagations downstream of large terrains. The improvements are still seen in many aspects such as the mean‐state precipitation when turning off the convection feedback impacts in the revised scheme, emphasizing the benefits of using the modified mass‐flux closure. However, the convection feedbacks have considerable effects on the precipitation diurnal cycle simulations over regions with late‐afternoon precipitation peaks. Overall, the revised scheme provides a unified treatment for sub‐grid vertical motions across regimes of boundary‐layer turbulence, shallow convection, and deep convection, leading to better‐simulated precipitation at various timescales.
Reading the Leaves to Track Environmental Hazards and Health
Authors: Crimmins Theresa
Published: April 2021

The USA National Phenology Network is small but mighty, helping scientists and resource managers assess natural hazards and seasonal phenomena that affect society in numerous ways.
Robust Inter‐Hemispheric Asymmetry in the Response to Symmetric Volcanic Forcing in Model Large Ensembles
Authors: Pauling Andrew G. , Bushuk Mitchell , Bitz Cecilia M.
Published: April 2021

The climate response to volcanic eruptions in the twentieth century is difficult to separate from the influence of anthropogenic greenhouse gas forcing and internal variability. Here, we make use of recently available large ensembles of Earth‐system model simulations to better understand the forced climate response to contemporary volcanic eruptions. While the Pinatubo eruption in June 1991 resulted in approximately symmetric forcing between the Northern and Southern Hemispheres, the ensemble‐mean simulated temperature and sea ice responses it produces are asymmetric. The strongest cooling and sea ice expansion occur in the Arctic, while the responses in the Antarctic are weak. The damped high‐latitude Southern Hemisphere response to volcanic forcing is analogous to the fast response to increased greenhouse gas concentrations, despite the differing physical nature of the forcing. We find that Arctic cooling in response to a Pinatubo‐scale eruption may not occur due to the high internal variability in that region
Contributions of Arctic Sea‐Ice Loss and East Siberian Atmospheric Blocking to 2020 Record‐Breaking Meiyu‐Baiu Rainfall
Authors: Chen Xiaodan , Dai Aiguo , Wen Zhiping , Song Yuanyuan
Published: April 2021

Heavy Meiyu‐Baiu rainfall occurred over central‐east China and Japan in June–July 2020. This study analyzes observational and reanalysis data and performs atmospheric model simulations to investigate its causes. It is found that low Arctic sea ice cover (SIC) in late spring‐early summer of 2020 along the Siberian coast was an important factor. The low SIC caused local warming and high pressure, resulted in excessive atmospheric blockings over East Siberia, which caused cold air outbreaks into the Meiyu‐Baiu region, stopped the seasonal northward march of the Meiyu‐Baiu front, and increased the thermal contrast across the front, leading to record‐breaking rainfall in June–July 2020. Our results suggest that the 2020 extreme Meiyu‐Baiu was partly caused by the low SIC around the Siberian coast through its impact on East Siberian blockings. As sea ice along the Siberian coast decreases under global warming, its variations and thus influence on Meiyu‐Baiu rainfall may weaken.
Altered relationship between subjective perception and central representation of touch hedonics in adolescents with autism-spectrum disorder
Authors: Perini Irene , Gustafsson Per A. , Igelström Kajsa , Jasiunaite-Jokubaviciene Brigita , Kämpe Robin , Mayo Leah M. , Molander Johanna , Olausson Håkan , Zetterqvist Maria , Heilig Markus
Published: April 2021

An impairment of social communication is a core symptom of autism-spectrum disorder (ASD). Affective touch is an important means of social interaction, and C-Tactile (CT) afferents are thought to play a key role in the peripheral detection and encoding of these stimuli. Exploring the neural and behavioral mechanisms for processing CT-optimal touch (~3 cm/s) may therefore provide useful insights into the pathophysiology of ASD. We examined the relationship between touch hedonics (i.e. the subjective pleasantness with which affective touch stimuli are perceived) and neural processing in the posterior superior temporal sulcus (pSTS). This region is less activated to affective touch in individuals with ASD, and, in typically developing individuals (TD), is correlated positively with touch pleasantness. TD and ASD participants received brushing stimuli at CT-optimal, and CT-non-optimal speeds during fMRI. Touch pleasantness and intensity ratings were collected, and affective touch awareness, a measure of general touch hedonics was calculated. As expected, slow touch was perceived as more pleasant and less intense than fast touch in both groups, whereas affective touch awareness was moderately higher in TD compared to ASD. There was a strong, positive correlation between right pSTS activation and affective touch awareness in TD, but not in ASD. Our findings suggest that altered neural coupling between right pSTS and touch hedonics in ASD may be associated with social touch avoidance in ASD.
Germline variants at SOHLH2 influence multiple myeloma risk
Authors: Duran-Lozano Laura , Thorleifsson Gudmar , Lopez de Lapuente Portilla Aitzkoa , Niroula Abhishek , Went Molly , Thodberg Malte , Pertesi Maroulio , Ajore Ram , Cafaro Caterina , Olason Pall I. , Stefansdottir Lilja , Bragi Walters G. , Halldorsson Gisli H. , Turesson Ingemar , Kaiser Martin F. , Weinhold Niels , Abildgaard Niels , Andersen Niels Frost , Mellqvist Ulf-Henrik , Waage Anders , Juul-Vangsted Annette , Thorsteinsdottir Unnur , Hansson Markus , Houlston Richard , Rafnar Thorunn , Stefansson Kari , Nilsson Björn
Published: April 2021

Multiple myeloma (MM) is caused by the uncontrolled, clonal expansion of plasma cells. While there is epidemiological evidence for inherited susceptibility, the molecular basis remains incompletely understood. We report a genome-wide association study totalling 5,320 cases and 422,289 controls from four Nordic populations, and find a novel MM risk variant at SOHLH2 at 13q13.3 (risk allele frequency = 3.5%; odds ratio = 1.38; P = 2.2 × 10−14). This gene encodes a transcription factor involved in gametogenesis that is normally only weakly expressed in plasma cells. The association is represented by 14 variants in linkage disequilibrium. Among these, rs75712673 maps to a genomic region with open chromatin in plasma cells, and upregulates SOHLH2 in this cell type. Moreover, rs75712673 influences transcriptional activity in luciferase assays, and shows a chromatin looping interaction with the SOHLH2 promoter. Our work provides novel insight into MM susceptibility.
Foxq1 promotes metastasis of nasopharyngeal carcinoma by inducing vasculogenic mimicry via the EGFR signaling pathway
Authors: Luo Yunfan , Wang Jie , Wang Fan , Liu Xiong , Lu Juan , Yu Xiaoxiao , Ma Xuemin , Peng Xiaohong , Li Xiangping
Published: April 2021

In nasopharyngeal carcinoma (NPC), the treatment of tumor metastasis and recurrence is challenging and is associated with poor clinical efficacy. Vasculogenic mimicry (VM) is a new blood-supply model of malignant tumor that is closely related to tumors’ distant metastasis. Our previous study demonstrated that miR-124 could target Foxq1 to inhibit NPC metastasis. Whether Foxq1 affects metastasis through vasculogenic mimicry is worth consideration. In this study, we show that VM formation positively correlates with the expression of Foxq1, and EGFR, and the TNM stage in 114 NPC patient samples. Meanwhile, we show that VM-positive NPC patients have a poor prognosis. Furthermore, using in vitro and vivo approaches, we confirm that Foxq1 has a significant effect on NPC metastasis through promoting VM formation, which could be effectively inhibited by EGFR inhibitors (Nimotuzumab or Erlotinib). Also a synergistic efficacy of anti-EGFR and anti-VEGF drugs has been found in NPC inhibition. Mechanistically, the luciferase reporter gene and CHIP assays show that Foxq1 directly binds to the EGFR promoter region and regulates EGFR transcription. In conclusion, our results show that Foxq1 is regulated by miR-124 and that it promotes NPC metastasis by inducing VM via the EGFR signaling pathway. Overall, these results provide a new theoretical support and a novel target selection for anti-VM therapy in the treatment of nasopharyngeal carcinoma.
CPA-seq reveals small ncRNAs with methylated nucleosides and diverse termini
Authors: Wang Heming , Huang Rong , Li Ling , Zhu Junjin , Li Zhihong , Peng Chao , Zhuang Xuran , Lin Haifan , Shi Shuo , Huang Pengyu
Published: April 2021

High-throughput sequencing reveals the complex landscape of small noncoding RNAs (sRNAs). However, it is limited by requiring 5′-monophosphate and 3′-hydroxyl in RNAs for adapter ligation and hindered by methylated nucleosides that interfere with reverse transcription. Here we develop Cap-Clip acid pyrophosphatase (Cap-Clip), T4 polynucleotide kinase (PNK) and AlkB/AlkB(D135S)-facilitated small ncRNA sequencing (CPA-seq) to detect and quantify sRNAs with terminus multiplicities and nucleoside methylations. CPA-seq identified a large number of previously undetected sRNAs. Comparison of sRNAs with or without AlkB/AlkB(D135S) treatment reveals nucleoside methylations on sRNAs. Using CPA-seq, we profiled the sRNA transcriptomes (sRNomes) of nine mouse tissues and reported the extensive tissue-specific differences of sRNAs. We also observed the transition of sRNomes during hepatic reprogramming. Knockdown of mesenchymal stem cell-enriched U1-5′ snsRNA promoted hepatic reprogramming. CPA-seq is a powerful tool with high sensitivity and specificity for profiling sRNAs with methylated nucleosides and diverse termini.