bluuebunny/crossref_metadata_2025 huggingface dataset:
Solid Swallow Examination During High Resolution Manometry and EGJ-Distensibility Help Identify Esophageal Outflow Obstruction in Non-obstructive Dysphagia
Authors: Murray Fritz Ruprecht , Fischbach Lara Maria , Schindler Valeria , Schnurre Larissa , Hente Juliane Marie , Tatu Aurora , Pohl Daniel
Published: February 2021

Single water swallow (SWS) high-resolution manometry (HRM) may miss relevant esophageal motility disorders. Solid test meal (STM) during HRM and lately the functional lumen imaging probe (FLIP) have been shown to be of diagnostic value in the assessment of motility disorders. We aimed to assess the diagnostic yield of STM and FLIP in non-obstructive dysphagia (NOD). Patients assessed for dysphagia with both HRM and FLIP between April 2016 and August 2019 were analyzed for signs of non-obstructive EGJ outflow obstruction (EGJOO) according to Chicago Classification 3.0 (CCv3) and CC adapted for the use with solid swallows (CC-S), followed by an individual group-specific analysis. Five subjects without dysphagia served as control group. Standard HRM- and FLIP-values as well as esophagograms and Eckardt Scores were analyzed. Forty-two patients were identified (male/female, 14/36, median age 62). Twenty-five (59.5%) were diagnosed with EGJOO during STM only (= SWS-negative patients; CC-S). The EGJ distensibility index (EGJ-DI) of symptomatic patients was significantly lower compared to the control group (p = 0.006). EGJ-DI was < 3mm2/mmHg in 67% and 88% of patients diagnosed according to CC-S and CCv3, respectively. The IRP during STM showed a significant association to the corresponding EGJ-DI values (p < 0.001). Seventy-six percent of patients received treatment because of additional STM evaluation with a favorable clinical response rate of 89%. STM and FLIP identify EGJOO in symptomatic patients with normal SWS during HRM. STM resembles an inexpensive and clinically meaningful option to diagnose motility disorders and helps to select patients for interventional treatment.
Web-based self-help intervention for partners of cancer patients based on acceptance and commitment therapy and self-compassion training: a randomized controlled trial with automated versus personal feedback
Authors: Köhle Nadine , Drossaert Constance H. C. , ten Klooster Peter M. , Schreurs Karlein M. G. , Hagedoorn Mariët , Van Uden-Kraan Cornelia F. , Verdonck-de Leeuw Irma M. , Bohlmeijer Ernst T.
Published: February 2021

Purpose

To evaluate the effectiveness of two versions (personal or automated feedback) of a psychological Web-based self-help intervention targeting partners of cancer patients. The intervention was based on acceptance and commitment therapy (ACT) and self-compassion training. Participants’ adherence and their satisfaction were also studied.

Methods

Two hundred three partners of patients with heterogeneous entities of cancer were randomized into three conditions: personal feedback (PF) (n = 67), automated feedback (AF) (n = 70), or waiting list (WL) control (n = 66). Participants completed measures at baseline (T0) and post-intervention (T1; 3 months after baseline) to assess psychological distress (HADS; primary outcome), positive mental health, caregiver strain, general health (secondary outcomes), posttraumatic growth, resilience, self-compassion, psychological flexibility, sense of mastery, and relational communication style (process measures). Participants in the two experimental conditions also completed these measures at follow-up (T2; 6 months after baseline).

Results

There was no significant difference in change in psychological distress, positive mental health, caregiver strain and general health from T0 to T1 for either of the experimental conditions compared with the WL-condition. However, when compared to a WL-condition, the PF-condition was effective in increasing psychological flexibility (effect size d = 0.49) and resilience (d = 0.12) and decreasing overprotection (d = 0.25), and the AF-condition was effective in reducing overprotection (d = 0.36) and improving protective buffering (d = 0.36). At follow-up, the PF-condition was more effective than the AF-condition for improving mental health (d = 0.36), psychological flexibility (d = 0.60), mastery (d = 0.48), and protective buffering (d = 0.24). Participants positively appreciated the intervention and 69% participants were adherent.

Conclusion

This study demonstrates that a Web-based intervention based on ACT and self-compassion training with automated or personal feedback does not seem to improve psychological distress; however, it may have the potential to support partners of cancer patients to cope with the difficult situation they are facing. The condition with personal feedback seemed to be more beneficial.
Age-related decline in the taurine content of the skin in rodents
Authors: Yoshimura Tomohisa , Inokuchi Yuki , Mutou Chikako , Sakurai Takanobu , Nagahama Tohru , Murakami Shigeru
Published: February 2021

Taurine, a sulfur-containing amino acid, occurs at high concentrations in the skin, and plays a role in maintaining the homeostasis of the skin. We investigated the effects of aging on the content and localization of taurine in the skin of mice and rats. Taurine was extracted from the skin samples of hairless mice and Sprague Dawley rats, and the taurine content of the skin was determined by high-performance liquid chromatography (HPLC). The results of the investigation revealed that the taurine content in both the dermis and epidermis of hairless mice declined significantly with age. Similar age-related decline in the skin taurine content was also observed in rats. In contrast, the taurine content in the sole remained unchanged with age. An immunohistochemical analysis also revealed a decreased skin taurine content in aged animals compared with younger animals, although no significant differences in the localization of taurine were observed between the two age groups. Supplementation of the drinking water of aged mice with 3% (w/v) taurine for 4 weeks increased the taurine content of the epidermis, but not the dermis. The present study showed for the first time that the taurine content of the skin decreased with age in mice and rats, which may be related to the impairment of the skin homeostasis observed with aging. The decreased taurine content of the epidermis in aged animals was able to be rescued by taurine supplementation.
Comparing symptoms, treatment patterns, and quality of life of ankylosing spondylitis and non-radiographic axial spondyloarthritis patients in the USA: findings from a patient and rheumatologist Survey
Authors: Hunter Theresa , Sandoval David , Booth Nicola , Holdsworth Elizabeth , Deodhar Atul
Published: February 2021

Objectives

The aim of this study was to compare the symptoms, treatment patterns, and quality of life (QoL) of ankylosing spondylitis (AS) patients to non-radiographic axial spondyloarthritis (nr-axSpA) patients in the USA.

Method

A cross-sectional survey was conducted with rheumatologists and their consulting patients in the USA from June through August 2018. Patients who had a rheumatologist confirmed diagnosis of AS and nr-axSpA were eligible to participate. Patient demographics, symptoms, and medication use were reported by the rheumatologist, while work disability and QoL measures were reported by the patient. Patient demographics, symptoms, QoL and treatment patterns of AS and nr-axSpA patients were compared using parametric tests and non-parametric tests when appropriate.

Results

A total of 515 AS patients and 495 nr-axSpA patients were included in this analysis. A higher proportion of AS patients were male (p < 0.001), older (p = 0.014), and more likely to be prescribed a biologic (p < 0.0001). On average, AS patients experienced slightly more symptoms at diagnosis (p = 0.023); however, nr-axSpA patients were more likely to experience enthesitis (p = 0.048) and synovitis (p = 0.003). Patient reported outcomes such as the ASAS Health Index (p = 0.171), ASQoL (p = 0.296), BASDAI (p = 0.124), and WPAI (p = 0.183) were similar between AS and nr-axSpA patients after adjusting for confounding variables such as medication use.

Conclusions

AS and nr-axSpA patients share the same clinical features. The burden of the disease, as assessed by QoL measurements, is also similar in AS and nr-axSpA patients; however, despite these similarities, patients with nr-axSpA are less likely to be treated with a biologic.

Key Points

• Ankylosing spondylitis and non• radiographic axial spondyloarthritis patients share similar clinical features and burden of disease.• Quality of life is similar among ankylosing spondylitis and non• radiographic axial spondyloarthritis after adjusting for current treatment patterns.
The impact of preoperative anxiety on patients undergoing brain surgery: a systematic review
Authors: Oteri Vittorio , Martinelli Anna , Crivellaro Elisa , Gigli Francesca
Published: February 2021

Preoperative anxiety is a common reaction exhibited by up to 80% of patients who are scheduled for surgical procedures and characterized by psychological and physical changes which may affect their perioperative period. Our aim is to report the most up-to-date evidence on preoperative anxiety in brain surgery patients through a systematic analysis of the studies produced in the last decades. We performed a systematic review of literature by searching PubMed, Embase, and Cochrane Library databases. Data were extracted using the Population, Intervention, Comparison, Outcome framework and critically analyzed. PRISMA guidelines were applied, and the risk of bias of the included studies was assessed using the Risk of bias (RoB) 2 and ROBINS tools, as was the methodological quality, following GRADE criteria. We included 27 articles, accounting for 2558 patients in twelve different countries. The prevalence of preoperative anxiety ranged from 17 up to 89%, higher in female patients. Preoperative anxiety was associated with lower quality of life and cognitive performance, higher need for information, poorer memory and attention, longer hospitalization, depressive symptoms, and increase of physical disability; no correlation with survival rate was found. Seven randomized controlled trials attested the efficacy of acupuncture, music therapy, virtual reality, and pharmacological support in lowering anxiety levels. Preoperative anxiety is a common phenomenon that could negatively affect the perioperative period of brain surgery patients: this is something that should not be neglected to achieve better care through early prevention and optimal management.
Perspektiven für die Haushaltspolitik der Europäischen Union
Authors:   Überblick
Published: February 2021

Die Europäische Union hat mit „NextGenerationEU“ (NGEU) einen Fonds aufgelegt, um die wirtschaftliche Erholung ihrer Mitgliedstaaten während und nach der Corona-Pandemie zu unterstützen. Mit dem Fonds sollen die Kohäsion sowie der grüne und digitale Wandel in Europa befördert werden. Gleichzeitig hat die EU ihre Haushaltsmittel im Rahmen des Mehrjährigen Finanzrahmens 2021 bis 2027 nur leicht erhöht. Die finanzielle Unterstützung durch die EU wird positiv bewertet. Allerdings bleibt fraglich, wo die nationalen Prioritäten liegen und ob die gesteckten Ziele tatsächlich strukturelle Veränderungen im Sinne der EU ermöglichen. In jedem Fall verändert NGEU die Finanzarchitektur der EU, da der Fonds über gemeinsame Anleihen finanziert werden soll. Welche Folgen dies für die Struktur der EU-Finanzen langfristig haben kann und welche Reformansätze sinnvoll sind, ist Gegenstand der Debatte.
Responsibility and the ‘Pie Fallacy’
Authors: Kaiserman Alex
Published: February 2021

Much of our ordinary thought and talk about responsibility exhibits what I call the ‘pie fallacy’—the fallacy of thinking that there is a fixed amount of responsibility for every outcome, to be distributed among all those, if any, who are responsible for it. The pie fallacy is a fallacy, I argue, because how responsible an agent is for some outcome is fully grounded in facts about the agent, the outcome and the relationships between them; it does not depend, in particular, on how responsible anyone else is for that same outcome. In this paper, I explore how the pie fallacy can arise by considering several different kinds of case in which two or more agents are responsible for the same outcome. I’ll end with some brief remarks on the potential consequences of my arguments for how to think about responsibility in war.
Fundamental mechanisms of the stem cell regulation in land plants: lesson from shoot apical cells in bryophytes
Authors: Hata Yuki , Kyozuka Junko
Published: February 2021

Key message

This review compares the molecular mechanisms of stem cell control in the shoot apical meristems of mosses and angiosperms and reveals the conserved features and evolution of plant stem cells.

The establishment and maintenance of pluripotent stem cells in the shoot apical meristem (SAM) are key developmental processes in land plants including the most basal, bryophytes. Bryophytes, such as Physcomitrium (Physcomitrella) patens and Marchantia polymorpha, are emerging as attractive model species to study the conserved features and evolutionary processes in the mechanisms controlling stem cells. Recent studies using these model bryophyte species have started to uncover the similarities and differences in stem cell regulation between bryophytes and angiosperms. In this review, we summarize findings on stem cell function and its regulation focusing on different aspects including hormonal, genetic, and epigenetic control. Stem cell regulation through auxin, cytokinin, CLAVATA3/EMBRYO SURROUNDING REGION-RELATED (CLE) signaling and chromatin modification by Polycomb Repressive Complex 2 (PRC2) and PRC1 is well conserved. Several transcription factors crucial for SAM regulation in angiosperms are not involved in the regulation of the SAM in mosses, but similarities also exist. These findings provide insights into the evolutionary trajectory of the SAM and the fundamental mechanisms involved in stem cell regulation that are conserved across land plants.
Comparison Principle for Elliptic Equations with Mixed Singular Nonlinearities
Authors: Durastanti Riccardo , Oliva Francescantonio
Published: February 2021

We deal with existence and uniqueness of positive solutions of an elliptic boundary value problem modeled by
$$ \left \{\begin {array}{ll} \displaystyle -{\Delta }_{p} u= \frac {f}{u^{\gamma }} + g u^{q} & \text { in } {\Omega }, \\ u = 0 & \text {on } \partial {\Omega }, \end {array}\right . $$

−

Δ

p

u
=

f

u

γ

+
g

u

q

in

Ω
,

u
=
0

on

∂
Ω
,

where Ω is an open bounded subset of $\mathbb {R}^{N}$

ℝ

N

where Ω is an open bounded subset of $\mathbb {R}^{N}$

ℝ

N

, Δpu := ÷(|∇u|p− 2∇u) is the usual p-Laplacian operator, γ ≥ 0 and 0 ≤ q ≤ p − 1; f and g are nonnegative functions belonging to suitable Lebesgue spaces.
An Integrative Systems Approach to Enhancing Service Delivery for Individuals with Complex Needs
Authors: Pei Jacqueline , Poth Cheryl , Tremblay Melissa , Walker Meghan
Published: February 2021

Purpose of Review

There are a lack of system-wide integrative services for individuals with complex needs and a corresponding demand for advancing cross-disciplinary practices in community settings. This demand is especially acute for individuals with fetal alcohol spectrum disorder (FASD) and a gap we have sought to address.

Recent Findings

We present findings from a literature scan to guide service delivery for individuals and families affected by FASD and other complex needs: four overarching guiding principles for policy decision-makers, seven guiding practices for organizations, and 23 guiding practices for service providers.

These identified principles and practices bridge diverse perspectives, with potential for their implementation to provide consistent, evidence-based services to underserved populations with complex needs.
Estimating Changes in Forest Attributes and Enhancing Growth Projections: a Review of Existing Approaches and Future Directions Using Airborne 3D Point Cloud Data
Authors: Tompalski Piotr , Coops Nicholas C. , White Joanne C. , Goodbody Tristan R.H. , Hennigar Chris R. , Wulder Michael A. , Socha Jarosław , Woods Murray E.
Published: February 2021

Purpose of Review

The increasing availability of three-dimensional point clouds, including both airborne laser scanning and digital aerial photogrammetry, allow for the derivation of forest inventory information with a high level of attribute accuracy and spatial detail. When available at two points in time, point cloud datasets offer a rich source of information for detailed analysis of change in forest structure.

Recent Findings

Existing research across a broad range of forest types has demonstrated that those analyses can be performed using different approaches, levels of detail, or source data. By reviewing the relevant findings, we highlight the potential that bi- and multi-temporal point clouds have for enhanced analysis of forest growth. We divide the existing approaches into two broad categories— – approaches that focus on estimating change based on predictions of two or more forest inventory attributes over time, and approaches for forecasting forest inventory attributes. We describe how point clouds acquired at two or more points in time can be used for both categories of analysis by comparing input airborne datasets, before discussing the methods that were used, and resulting accuracies.

To conclude, we outline outstanding research gaps that require further investigation, including the need for an improved understanding of which three-dimensional datasets can be applied using certain methods. We also discuss the likely implications of these datasets on the expected outcomes, improvements in tree-to-tree matching and analysis, integration with growth simulators, and ultimately, the development of growth models driven entirely with point cloud data.
Why current quantitative serology is not quantitative and how systems immunology could provide solutions
Authors: Prechl József
Published: February 2021

Determination of the presence of antibodies against infectious agents, self-antigens, allogeneic antigens and environmental antigens is the goal of medical serology. Along with the standardization of these tests the community also started to use the expression “quantitative serology,” referring to the fact that arbitrary units are used for the expression of results. In this review I will argue against the use of the term quantitative serology for current tests. Because each test and each antibody isotype determination uses its own references, the term semiquantitative better describes these methods. The introduction of really quantitative serology could both benefit from and drive forward systems immunological approach to immunity.
Ketamine—50 years in use: from anesthesia to rapid antidepressant effects and neurobiological mechanisms
Authors: Kohtala Samuel
Published: February 2021

Over the past 50 years, ketamine has solidified its position in both human and veterinary medicine as an important anesthetic with many uses. More recently, ketamine has been studied and used for several new indications, ranging from chronic pain to drug addiction and post-traumatic stress disorder. The discovery of the rapid-acting antidepressant effects of ketamine has resulted in a surge of interest towards understanding the precise mechanisms driving its effects. Indeed, ketamine may have had the largest impact for advancements in the research and treatment of psychiatric disorders in the past few decades. While intense research efforts have been aimed towards uncovering the molecular targets underlying ketamine’s effects in treating depression, the underlying neurobiological mechanisms remain elusive. These efforts are made more difficult by ketamine’s complex dose-dependent effects on molecular mechanisms, multiple pharmacologically active metabolites, and a mechanism of action associated with the facilitation of synaptic plasticity. This review aims to provide a brief overview of the different uses of ketamine, with an emphasis on examining ketamine’s rapid antidepressant effects spanning molecular, cellular, and network levels. Another focus of the review is to offer a perspective on studies related to the different doses of ketamine used in antidepressant research. Finally, the review discusses some of the latest hypotheses concerning ketamine’s action.
Challenges for the management of the invasive blackberry (Rubus niveus) in the restoration of the Scalesia forest in the Galapagos Islands
Authors: Renteria Jorge L. , Atkinson Rachel , Crespo Claudio , Gardener Mark R. , Grosholz Edwin D.
Published: February 2021

Strong competitive ability of introduced plant species has been frequently stated as a key factor promoting successful invasion. The dynamics of invasive species may depend on their abilities to compete for resources and exploit disturbances relative to native species. This study compares the growth performance of the invasive blackberry (Rubus niveusThunb.) with four of the most common woody native species of the Scalesia forest in the Galapagos Islands. Using a series of greenhouse and field studies, the growth rate and biomass production of native species alone and in competition withR. niveuswas compared under different water and light stress conditions.Rubus niveusshowed a faster growth rate and biomass production than the native species as well as a broad tolerance to light and water stress conditions. Competitive ability was also assessed by looking at the seedbank and regeneration processes after herbicide control in the field. Although the number ofR. niveusseedlings that germinated from the soil samples was considerably larger than that of native species, recruitment of the invasive on the experimental plots was limited. Overall,R. niveusshowed superior competitive ability over native species with comparable growth forms, suggesting a possible mechanism that enablesR. niveusto successfully invade a wide range of habitats in the Galapagos Islands. Implementing an integrated management strategy including biological control, seedbank reduction, and active revegetation, should improve the efficiency ofR. niveusmanagement, enabling the restoration of degraded vegetation in the Galapagos.
Investigation of Small‐Scale Electron Density Irregularities Observed by the Arase and Van Allen Probes Satellites Inside and Outside the Plasmasphere
Authors: Thomas Neethal , Shiokawa Kazuo , Miyoshi Yoshizumi , Kasahara Yoshiya , Shinohara Iku , Kumamoto Atsushi , Tsuchiya Fuminori , Matsuoka Ayako , Kasahara Satoshi , Yokota Shoichiro , Keika Kunihiro , Hori Tomoaki , Asamura Kazushi , Wang Shiang‐Yu , Kazama Yoichi , Tam Sunny Wing‐Yee , Chang Tzu‐Fang , Wang Bo‐Jhou , Wygant John , Breneman Aaron , Reeves Geoffrey
Published: February 2021

In situ electron density profiles obtained from Arase in the night magnetic local time (MLT) sector and from RBSP‐B covering all MLTs are used to study the small‐scale density irregularities present in the plasmasphere and near the plasmapause. Electron density perturbations with amplitudes >10% from background density and with time‐scales less than 30‐min are investigated here as the small‐scale density irregularities. The statistical survey of the density irregularities is carried out using nearly 2 years of density data obtained from RBSP‐B and 4 months of data from Arase satellites. The results show that density irregularities are present globally at all MLT sectors and L‐shells both inside and outside the plasmapause, with a higher occurrence at L > 4. The occurrence of density irregularities is found to be higher during disturbed geomagnetic and interplanetary conditions. The case studies presented here revealed: (1) The plasmaspheric density irregularities observed during both quiet and disturbed conditions are found to coexist with the hot plasma sheet population. (2) During quiet periods, the plasma waves in the whistler‐mode frequency range are found to be modulated by the small‐scale density irregularities, with density depletions coinciding well with the decrease in whistler intensity. Our observations suggest that different source mechanisms are responsible for the generation of density structures at different MLTs and geomagnetic conditions.
Towards a Multi‐Platform Assimilative System for North Sea Biogeochemistry
Authors: Skákala Jozef , Ford David , Bruggeman Jorn , Hull Tom , Kaiser Jan , King Robert R. , Loveday Benjamin , Palmer Matthew R. , Smyth Tim , Williams Charlotte A. J. , Ciavatta Stefano
Published: February 2021

Oceanography has entered an era of new observing platforms, such as biogeochemical‐Argo floats and gliders, some of which will provide three‐dimensional maps of essential ecosystem variables on the North‐West European (NWE) Shelf. In a foreseeable future operational centers will use multi‐platform assimilation to integrate those valuable data into ecosystem reanalysis and forecast systems. Here we address some important questions related to glider biogeochemical data assimilation (DA) and introduce multi‐platform DA in a preoperational model of the NWE Shelf sea ecosystem. We test the impact of the different multi‐platform system components (glider vs. satellite, physical vs. biogeochemical) on the simulated biogeochemical variables. To characterize the model performance, we focus on the period around the phytoplankton spring bloom, since the bloom is a major ecosystem driver on the NWE Shelf. We found that the timing and magnitude of the phytoplankton bloom is insensitive to the physical DA, which is explained in the study. To correct the simulated phytoplankton bloom one needs to assimilate chlorophyll observations from glider or satellite Ocean Color (OC) into the model. Although outperformed by the glider chlorophyll assimilation, we show that OC assimilation has mostly desirable impact on the sub‐surface chlorophyll. Since the OC assimilation updates chlorophyll only in the mixed layer, the impact on the sub‐surface chlorophyll is the result of the model dynamical response to the assimilation. We demonstrate that the multi‐platform assimilation combines the advantages of its components and always performs comparably to its best performing component.
Paleoecology of Late Cretaceous Coccolithophores: Insights From the Shallow‐Marine Record
Authors: Püttmann Tobias , Mutterlose Jörg
Published: February 2021

Coccolithophores, common primary producers in Mesozoic, Cenozoic, and present oceans, are significant components of the earth’s biogeochemical cycles. Being the most productive calcifying organism on earth, their carbonate oozes play a major role in fixing CO2, thereby forming the most important long‐term CO2 sink throughout the last 100 Ma. Our understanding of their fossil ancestors is mainly based on data from chalk sequences. Generally, the Cretaceous chalks were deposited at water depths of ≥200 m under stable, pelagic conditions. Here we report on remarkably diverse fossil coccolithophore assemblages from Cenomanian‐Campanian (100‐72 Ma) nearshore deposits, with estimated water depths of ≤40 m. For interpreting the findings in a broader paleoenvironmental context, we additionally analyzed contemporaneous chalk material from the Santonian‐Campanian (86‐72 Ma) interval. Highly diverse coccolithophore associations (50–81 species/sample) characterize the nearshore setting, while the contemporaneous chalk samples are less diverse (43–54 species/sample). The absolute abundances of coccoliths from the nearshore setting are by a factor 2–10 lower than those from the chalk, diversity indices are by 20%–30% higher (Shannon Index = 2.94–3.46) in the nearshore sediments. The presence of highly diverse coccolithophore communities in nearshore settings provides new insights into their paleoecology and evolution and the paleoceanography of the Late Cretaceous. Our data revise the traditional view of coccolithophores being typical open ocean dwellers. Extreme nearshore settings of the Late Cretaceous greenhouse world were characterized by environmental conditions equating those of the hemipelagic realm but supplying a larger variety of ecological niches.
Unbiased Estimates and Confidence Intervals for Riverine Loads
Authors: Tada Akio , Tanakamaru Haruya
Published: February 2021

Estimating the uncertainty in annual riverine constituent loads, which is the mass that passes through a river cross‐section into a receiving water body, using infrequent water quality (WQ) observations is a difficult and unsolved task. Therefore, we propose an unbiased point estimation method and interval estimation method for river loads based on the rating curve (RC) method using importance sampling and the bootstrap method, respectively. In this paper, we first statistically explain the unbiasedness of load estimates using the proposed method. Second, the effectiveness of point and interval estimates by the proposed method is demonstrated for river loads from a small catchment and from large watersheds based on discharge and WQ data of solutes, nutrients, and suspended sediments with 10‐min to daily intervals. The results show that the proposed method provides unbiased estimates and appropriate coverage of confidence intervals regardless of the RC model used. The results also reveal that the dominant cause of bias in load estimates based on ordinary RC methods, such as the Loadest model, is not due to the poor simulation of observed loading rates by the RCs or because of the nonnormality of the regression residuals but rather improper sampling strategies. The proposed method is currently not feasible for WQ monitoring sites in large rivers due to the unmanageability of missing observations or censored data and an inefficient sampling strategy, although the requirement of unbiased estimation explained here can aid in scheduling high‐flow sampling for monitoring sites.
Weighing Inputs of Waves and Precipitation to Coastal Erosion
Authors: Carmichael Jady
Published: February 2021

Conducting weekly lidar surveys of coastal cliffs for 3 years enabled a California team of coastal erosion researchers to quantify and separate marine effects from subaerial effects.
A modular hierarchical array camera
Authors: Yuan Xiaoyun , Ji Mengqi , Wu Jiamin , Brady David J. , Dai Qionghai , Fang Lu
Published: February 2021

Array cameras removed the optical limitations of a single camera and paved the way for high-performance imaging via the combination of micro-cameras and computation to fuse multiple aperture images. However, existing solutions use dense arrays of cameras that require laborious calibration and lack flexibility and practicality. Inspired by the cognition function principle of the human brain, we develop an unstructured array camera system that adopts a hierarchical modular design with multiscale hybrid cameras composing different modules. Intelligent computations are designed to collaboratively operate along both intra- and intermodule pathways. This system can adaptively allocate imagery resources to dramatically reduce the hardware cost and possesses unprecedented flexibility, robustness, and versatility. Large scenes of real-world data were acquired to perform human-centric studies for the assessment of human behaviours at the individual level and crowd behaviours at the population level requiring high-resolution long-term monitoring of dynamic wide-area scenes.
Correction to: Central IGF1 improves glucose tolerance and insulin sensitivity in mice
Authors: Hong Hao , Cui Zhen-Zhong , Zhu Lu , Fu Shu-Ping , Rossi Mario , Cui Ying-Hong , Zhu Bing-Mei
Published: February 2021

A Correction to this paper has been published: https://doi.org/10.1038/s41387-021-00153-4
Physiological dead space and alveolar ventilation in ventilated infants
Authors: Williams Emma , Dassios Theodore , Dixon Paul , Greenough Anne
Published: February 2021

Background

Dead space is the volume not taking part in gas exchange and, if increased, could affect alveolar ventilation if there is too low a delivered volume. We determined if there were differences in dead space and alveolar ventilation in ventilated infants with pulmonary disease or no respiratory morbidity.

Methods

A prospective study of mechanically ventilated infants was undertaken. Expiratory tidal volume and carbon dioxide levels were measured. Volumetric capnograms were constructed to calculate the dead space using the modified Bohr–Enghoff equation. Alveolar ventilation (VA) was also calculated.

Results

Eighty-one infants with a median (range) gestational age of 28.7 (22.4–41.9) weeks were recruited. The dead space [median (IQR)] was higher in 35 infants with respiratory distress syndrome (RDS) [5.7 (5.1–7.0) ml/kg] and in 26 infants with bronchopulmonary dysplasia (BPD) [6.4 (5.1–7.5) ml/kg] than in 20 term controls with no respiratory disease [3.5 (2.8–4.2) ml/kg, p < 0.001]. Minute ventilation was higher in both infants with RDS or BPD compared to the controls. VA in infants with RDS or BPD was similar to that of the controls [p = 0.54].

Conclusion

Prematurely born infants with pulmonary disease have a higher dead space than term controls, which may influence the optimum level during volume-targeted ventilation.

Impact

Measurement of the dead space was feasible in ventilated newborn infants.

The physiological dead space was a significant proportion of the delivered volume in ventilated infants.

The dead space (per kilogram) was higher in ventilated infants with respiratory distress syndrome or evolving bronchopulmonary dysplasia compared to term controls without respiratory disease.

The dead space volume should be considered when calculating the most appropriate volume during volume-targeted ventilation.
PLA2R1 promotes DNA damage and inhibits spontaneous tumor formation during aging
Authors: Huna Anda , Griveau Audrey , Vindrieux David , Jaber Sara , Flaman Jean-Michel , Goehrig Delphine , Azzi Lamia , Médard Jean-Jacques , Djebali Sophia , Hernandez-Vargas Hector , Dante Robert , Payen Léa , Marvel Jacqueline , Bertolino Philippe , Aubert Sébastien , Dubus Pierre , Bernard David
Published: February 2021

Although aging is a major risk factor for most types of cancers, it is barely studied in this context. The transmembrane protein PLA2R1 (phospholipase A2 receptor) promotes cellular senescence, which can inhibit oncogene-induced tumor initiation. Functions and mechanisms of action of PLA2R1 during aging are largely unknown. In this study, we observed that old Pla2r1 knockout mice were more prone to spontaneously develop a wide spectrum of tumors compared to control littermates. Consistently, these knockout mice displayed increased Parp1, a master regulator of DNA damage repair, and decreased DNA damage, correlating with large human dataset analysis. Forced PLA2R1 expression in normal human cells decreased PARP1 expression, induced DNA damage and subsequent senescence, while the constitutive expression of PARP1 rescued cells from these PLA2R1-induced effects. Mechanistically, PARP1 expression is repressed by a ROS (reactive oxygen species)-Rb-dependent mechanism upon PLA2R1 expression. In conclusion, our results suggest that PLA2R1 suppresses aging-induced tumors by repressing PARP1, via a ROS–Rb signaling axis, and inducing DNA damage and its tumor suppressive responses.
Selective killing of cancer cells harboring mutant RAS by concomitant inhibition of NADPH oxidase and glutathione biosynthesis
Authors: Liu Muyun , Wang Dan , Luo Yongde , Hu Lianghao , Bi Yawei , Ji Juntao , Huang Haojie , Wang Guoqiang , Zhu Liang , Ma Jianjia , Kim Eunice , Luo Catherine K. , Abbruzzese James L. , Li Xiaokun , Yang Vincent W. , Li Zhaoshen , Lu Weiqin
Published: February 2021

Oncogenic RAS is a critical driver for the initiation and progression of several types of cancers. However, effective therapeutic strategies by targeting RAS, in particular RASG12D and RASG12V, and associated downstream pathways have been so far unsuccessful. Treatment of oncogenic RAS-ravaged cancer patients remains a currently unmet clinical need. Consistent with a major role in cancer metabolism, oncogenic RAS activation elevates both reactive oxygen species (ROS)-generating NADPH oxidase (NOX) activity and ROS-scavenging glutathione biosynthesis. At a certain threshold, the heightened oxidative stress and antioxidant capability achieve a higher level of redox balance, on which cancer cells depend to gain a selective advantage on survival and proliferation. However, this prominent metabolic feature may irrevocably render cancer cells vulnerable to concurrent inhibition of both NOX activity and glutathione biosynthesis, which may be exploited as a novel therapeutic strategy. In this report, we test this hypothesis by treating the HRASG12V-transformed ovarian epithelial cells, mutant KRAS-harboring pancreatic and colon cancer cells of mouse and human origins, as well as cancer xenografts, with diphenyleneiodonium (DPI) and buthionine sulfoximine (BSO) combination, which inhibit NOX activity and glutathione biosynthesis, respectively. Our results demonstrate that concomitant targeting of NOX and glutathione biosynthesis induces a highly potent lethality to cancer cells harboring oncogenic RAS. Therefore, our studies provide a novel strategy against RAS-bearing cancers that warrants further mechanistic and translational investigation.
BMP2-dependent gene regulatory network analysis reveals Klf4 as a novel transcription factor of osteoblast differentiation
Authors: Yu Shuaitong , Guo Jinqiang , Sun Zheyi , Lin Chujiao , Tao Huangheng , Zhang Qian , Cui Yu , Zuo Huanyan , Lin Yuxiu , Chen Shuo , Liu Huan , Chen Zhi
Published: February 2021

Transcription factors (TFs) regulate the expression of target genes, inducing changes in cell morphology or activities needed for cell fate determination and differentiation. The BMP signaling pathway is widely regarded as one of the most important pathways in vertebrate skeletal biology, of which BMP2 is a potent inducer, governing the osteoblast differentiation of bone marrow stromal cells (BMSCs). However, the mechanism by which BMP2 initiates its downstream transcription factor cascade and determines the direction of differentiation remains largely unknown. In this study, we used RNA-seq, ATAC-seq, and animal models to characterize the BMP2-dependent gene regulatory network governing osteoblast lineage commitment. Sp7-Cre; Bmp2fx/fx mice (BMP2-cKO) were generated and exhibited decreased bone density and lower osteoblast number (n > 6). In vitro experiments showed that BMP2-cKO mouse bone marrow stromal cells (mBMSCs) had an impact on osteoblast differentiation and deficient cell proliferation. Osteogenic medium induced mBMSCs from BMP2-cKO mice and control were subjected to RNA-seq and ATAC-seq analysis to reveal differentially expressed TFs, along with their target open chromatin regions. Combined with H3K27Ac CUT&Tag during osteoblast differentiation, we identified 2338 BMP2-dependent osteoblast-specific active enhancers. Motif enrichment assay revealed that over 80% of these elements were directly targeted by RUNX2, DLX5, MEF2C, OASIS, and KLF4. We deactivated Klf4 in the Sp7 + lineage to validate the role of KLF4 in osteoblast differentiation of mBMSCs. Compared to the wild-type, Sp7-Cre; Klf4fx/+ mice (KLF4-Het) were smaller in size and had abnormal incisors resembling BMP2-cKO mice. Additionally, KLF4-Het mice had fewer osteoblasts and decreased osteogenic ability. RNA-seq and ATAC-seq revealed that KLF4 mainly “co-bound” with RUNX2 to regulate downstream genes. Given the significant overlap between KLF4- and BMP2-dependent NFRs and enriched motifs, our findings outline a comprehensive BMP2-dependent gene regulatory network specifically governing osteoblast differentiation of the Sp7 + lineage, in which Klf4 is a novel transcription factor.
Distinct functions of transforming growth factor-β signaling in c-MYC driven hepatocellular carcinoma initiation and progression
Authors: Wang Haichuan , Wang Pan , Xu Meng , Song Xinhua , Wu Hong , Evert Matthias , Calvisi Diego F. , Zeng Yong , Chen Xin
Published: February 2021

Dysregulation of transforming growth factor-beta (TGFβ) signaling has been implicated in liver carcinogenesis with both tumor promoting and inhibiting activities. Activation of the c-MYC protooncogene is another critical genetic event in hepatocellular carcinoma (HCC). However, the precise functional crosstalk between c-MYC and TGFβ signaling pathways remains unclear. In the present investigation, we investigated the expression of TGFβ signaling in c-MYC amplified human HCC samples as well as the mechanisms whereby TGFβ modulates c-Myc driven hepatocarcinogenesis during initiation and progression. We found that several TGFβ target genes are overexpressed in human HCCs with c-MYC amplification. In vivo, activation of TGFβ1 impaired c-Myc murine HCC initiation, whereas inhibition of TGFβ pathway accelerated this process. In contrast, overexpression of TGFβ1 enhanced c-Myc HCC progression by promoting tumor cell metastasis. Mechanistically, activation of TGFβ promoted tumor microenvironment reprogramming rather than inducing epithelial-to-mesenchymal transition during HCC progression. Moreover, we identified PMEPA1 as a potential TGFβ1 target. Altogether, our data underline the divergent roles of TGFβ signaling during c-MYC induced HCC initiation and progression.
Distinct Ring1b complexes defined by DEAD-box helicases and EMT transcription factors synergistically enhance E-cadherin silencing in breast cancer
Authors: Wang Yawei , Sun Yingying , Shang Chao , Chen Lili , Chen Hongyu , Wang Dake , Zeng Xianlu
Published: February 2021

Ring1b is a core subunit of polycomb repressive complex 1 (PRC1) and is essential in several high-risk cancers. However, the epigenetic mechanism of Ring1b underlying breast cancer malignancy is poorly understood. In this study, we showed increased expression of Ring1b promoted metastasis by weakening cell–cell adhesions of breast cancer cells. We confirmed that Ring1b could downregulate E-cadherin and contributed to an epigenetic rewiring via PRC1-dependent function by forming distinct complexes with DEAD-box RNA helicases (DDXs) or epithelial-mesenchymal transition transcription factors (EMT TFs) on site-specific loci of E-cadherin promoter. DDXs-Ring1b complexes moderately inhibited E-cadherin, which resulted in an early hybrid EMT state of epithelial cells, and EMT TFs-Ring1b complexes cooperated with DDXs-Ring1b complexes to further repress E-cadherin in mesenchymal-like cancer cells. Clinically, high expression of Ring1b with DDXs or EMT TFs predicted low levels of E-cadherin, metastatic behavior, and poor prognosis. These findings provide an epigenetic regulation mechanism of Ring1b complexes in E-cadherin expression. Ring1b complexes may be potential therapeutic targets and biomarkers for diagnosis and prognosis in invasion breast cancer.
Structural characterization of ice XIX as the second polymorph related to ice VI
Authors: Gasser Tobias M. , Thoeny Alexander V. , Fortes A. Dominic , Loerting Thomas
Published: February 2021

Ice polymorphs usually appear as hydrogen disorder-order pairs. Ice VI has a wide range of thermodynamic stability and exists in the interior of Earth and icy moons. Our previous work suggested ice β-XV as a second polymorph deriving from disordered ice VI, in addition to ice XV. Here we report thermal and structural characterization of the previously inaccessible deuterated polymorph using ex situ calorimetry and high-resolution neutron powder diffraction. Ice β-XV, now called ice XIX, is shown to be partially antiferroelectrically ordered and crystallising in a √2×√2×1 supercell. Our powder data recorded at subambient pressure fit best to the structural model in space group $$P\bar 4$$
P

4

¯

. Key to the synthesis of deuterated ice XIX is the use of a DCl-doped D2O/H2O mixture, where the small H2O fraction enhances ice XIX nucleation kinetics. In addition, we observe the transition from ice XIX to its sibling ice XV upon heating, which proceeds via a transition state (ice VI‡) containing a disordered H-sublattice. To the best of our knowledge this represents the first order-order transition known in ice physics.
Real-space imaging of acoustic plasmons in large-area graphene grown by chemical vapor deposition
Authors: Menabde Sergey G. , Lee In-Ho , Lee Sanghyub , Ha Heonhak , Heiden Jacob T. , Yoo Daehan , Kim Teun-Teun , Low Tony , Lee Young Hee , Oh Sang-Hyun , Jang Min Seok
Published: February 2021

An acoustic plasmon mode in a graphene-dielectric-metal structure has recently been spotlighted as a superior platform for strong light-matter interaction. It originates from the coupling of graphene plasmon with its mirror image and exhibits the largest field confinement in the limit of a sub-nm-thick dielectric. Although recently detected in the far-field regime, optical near-fields of this mode are yet to be observed and characterized. Here, we demonstrate a direct optical probing of the plasmonic fields reflected by the edges of graphene via near-field scattering microscope, revealing a relatively small propagation loss of the mid-infrared acoustic plasmons in our devices that allows for their real-space mapping at ambient conditions even with unprotected, large-area graphene grown by chemical vapor deposition. We show an acoustic plasmon mode that is twice as confined and has 1.4 times higher figure of merit in terms of the normalized propagation length compared to the graphene surface plasmon under similar conditions. We also investigate the behavior of the acoustic graphene plasmons in a periodic array of gold nanoribbons. Our results highlight the promise of acoustic plasmons for graphene-based optoelectronics and sensing applications.
Thermodynamics of structure-forming systems
Authors: Korbel Jan , Lindner Simon David , Hanel Rudolf , Thurner Stefan
Published: February 2021

Structure-forming systems are ubiquitous in nature, ranging from atoms building molecules to self-assembly of colloidal amphibolic particles. The understanding of the underlying thermodynamics of such systems remains an important problem. Here, we derive the entropy for structure-forming systems that differs from Boltzmann-Gibbs entropy by a term that explicitly captures clustered states. For large systems and low concentrations the approach is equivalent to the grand-canonical ensemble; for small systems we find significant deviations. We derive the detailed fluctuation theorem and Crooks’ work fluctuation theorem for structure-forming systems. The connection to the theory of particle self-assembly is discussed. We apply the results to several physical systems. We present the phase diagram for patchy particles described by the Kern-Frenkel potential. We show that the Curie-Weiss model with molecule structures exhibits a first-order phase transition.
Gold(I)-catalyzed intramolecular cyclization/intermolecular cycloaddition cascade as a fast track to polycarbocycles and mechanistic insights
Authors: Zhang Cheng , Hong Kemiao , Pei Chao , Zhou Su , Hu Wenhao , Hashmi A. Stephen K. , Xu Xinfang
Published: February 2021

Metal carbene is an active synthetic intermediate, which has shown versatile applications in synthetic chemistry. Although a variety of catalytic methods have been disclosed for the generation of carbene species from different precursors, there is an increasing demand for the development of efficient and practical approaches for the in-situ formation of metal carbene intermediates with structural diversity and unrevealed reactivity. Herein we report a gold-catalyzed cascade protocol for the assembly of polycarbocyclic frameworks in high yields under mild reaction conditions. Mechanistic studies indicate that the unique β-aryl gold-carbene species, generated via gold-promoted 6-endo-dig diazo-yne cyclization, is the key intermediate in this reaction, followed by a [4 + 2]-cycloaddition with external alkenes. In comparison to the well-documented metal carbene cycloadditions, this carbene intermediate serves as a 4-C synthon in a cycloaddition reaction. A variety of elusive π-conjugated polycyclic hydrocarbons (CPHs) with multiple substituents are readily accessible from the initially generated products by a mild oxidation procedure.