bluuebunny/crossref_metadata_2025 huggingface dataset:
Epidemiology of hospitalizations due to pesticide intoxication-associated acute kidney injury in China
Authors: He Min , Wu Yanhua , Xie Zhen , Li Zhilian , Hao Li , Liu Guohui , He Qiang , Liao Yuanjiang , Ghappar Rizwangul , Peng Hongwei , Xie Jinglie , Wei Xiaohong , Zhang Yusheng , Huang Qiongyi , Chen Yuanhan , Liang Xinling ,   China collaborative study on AKI (CCS-AKI)
Published: May 2021

Background

There is a paucity of epidemiological data regarding pesticide intoxication-associated acute kidney injury (AKI). Therefore, the aim of this study was to identify the epidemiological features, risk factors, and adverse outcomes of AKI in this population.

Methods

The data used in this multi-center, hospitalized population-based, retrospective study were retrieved from electronic medical records. AKI was defined as an acute increase in serum creatinine according to the criteria of Kidney Disease: Improving Global Outcomes. The Charlson Comorbidity Index was used to evaluate the burden of in-hospital mortality.

Results

Of 3,371 adult patients in 11 hospitals, 398 (11.8%) were diagnosed with AKI (grade 1, 218 [6.5%]; grade 2, 89 [2.6%]; grade 3, 91 [2.7%]). Herbicide intoxication was associated with the highest incidence of AKI (53.5%) and higher grades of AKI. After multivariable adjustment, pesticide categories and moderate or severe renal disease were independently associated with AKI. As compared with the referred category, insecticide and herbicide intoxications were associated with a 1.3-fold (95% CI 1.688–3.245) and 3.8-fold (95% CI 3.537–6.586) greater risk of AKI. Regardless of the pesticide category, AKI was independently associated with in-hospital mortality, with odds ratios of 3.433 (95% CI 1.436–8.203) for insecticides, 2.153 (95% CI 1.377–3.367) for herbicides, and 4.524 (95% CI 1.230–16.632) for unclassified or other pesticides.

Conclusion

AKI is common in pesticide intoxication and associated with an increased in-hospital mortality. Herbicides pose the greatest risks of AKI and death.
Interfacial Phenomena and Inclusion Formation Behavior at Early Melting Stages of HCFeCr and LCFeCr Alloys in Liquid Iron
Authors: Wang Yong , Karasev Andrey , Park Joo Hyun , Mu Wangzhong , Jönsson Pär G.
Published: May 2021

Chromium is normally added to liquid alloy in the form of different grades of ferrochromium (FeCr) alloys for the requirement of different alloy grades, such as stainless steels, high Cr cast iron, etc.. In this work, inclusions in two commercially produced alloys, i.e., high-carbon ferrochromium (HCFeCr) and low-carbon ferrochromium (LCFeCr) alloys, were investigated. The FeCr alloy/liquid iron interactions at an early stage were investigated by inserting solid alloy piece into contact with the liquid iron for a predetermined time using the liquid-metal-suction method. After quenching these samples, a diffusion zone between the alloys and the liquid Fe was studied based on the microstructural characterizations. It was observed that Cr-O-(Fe) inclusions were formed in the diffusion zone, FeO
x
inclusions were formed in the bulk Fe, and an “inclusion-free” zone was detected between them. Moreover, it was found that the HCFeCr was slowly dissolved, but LCFeCr alloy was rapidly melted during the experiment. The dissolution and melting behaviors of these two FeCr alloys were compared and the mechanism of the early-stage dissolution process of FeCr alloys in the liquid Fe was proposed.
Sexual, bladder and bowel function following different minimally invasive techniques of radical hysterectomy in patients with early-stage cervical cancer
Authors: Baessler K. , Windemut S. , Chiantera V. , Köhler C. , Sehouli J.
Published: May 2021

Purpose

Despite the establishment of radical surgery for therapy of cervical cancer, data on quality of life and patient-reported outcomes are scarce. The aim of this retrospective cohort study was to evaluate bladder, bowel and sexual function in women who underwent minimally invasive surgery for early-stage cervical cancer.

Methods

From 2007–2013, 261 women underwent laparoscopically assisted radical vaginal hysterectomy (LARVH = 45), vaginally assisted laparoscopic or robotic radical hysterectomy (VALRRH = 61) or laparoscopic total mesometrial resection (TMMR = 25) and 131 of them completed the validated German version of the Australian Pelvic Floor Questionnaire (PFQ). Results were compared with controls recruited from gynecological clinics (n = 24) and with urogynecological patients (n = 63).

Results

Groups were similar regarding age, BMI and parity. The TMMR group had significantly shorter median follow-up (16 months versus 70 and 36 months). Postoperatively, deterioration of bladder function was reported by 70%, 57% and 44% in the LARVH, VARRVH and TMMR groups, respectively (p = 0.734). Bowel function was significantly worse after TMMR with a higher deterioration rate in 72 versus 43% (LARVH) and 47% (VARRVH) with a correspondingly higher bowel dysfunction score of 2.9 versus 1.5 and 1.8, respectively and 1.8 in urogynaecological patients. Sexual dysfunction was common in all surgical groups. 38% considered their vagina too short which was significantly associated with deep dyspareunia.

Compared with controls, surgical groups had significantly increased PFQ scores.

Conclusion

Pelvic floor dysfunction commonly deteriorates and negatively impacts on quality of life after minimally invasive radical hysterectomy, especially bowel function after TMMR. Pelvic floor symptoms should routinely be addressed pre- and postoperatively.
Design and characterization of effective solar cells
Authors: Ojha Varun , Jansen Giorgio , Patanè Andrea , La Magna Antonino , Romano Vittorio , Nicosia Giuseppe
Published: May 2021

We propose a two-stage multi-objective optimization framework for full scheme solar cell structure design and characterization, cost minimization and quantum efficiency maximization. We evaluated structures of 15 different cell designs simulated by varying material types and photodiode doping strategies. At first, non-dominated sorting genetic algorithm II (NSGA-II) produced Pareto-optimal-solutions sets for respective cell designs. Then, on investigating quantum efficiencies of all cell designs produced by NSGA-II, we applied a new multi-objective optimization algorithm II (OptIA-II) to discover the Pareto fronts of select (three) best cell designs. Our designed OptIA-II algorithm improved the quantum efficiencies of all select cell designs and reduced their fabrication costs. We observed that the cell design comprising an optimally doped zinc-oxide-based transparent conductive oxide (TCO) layer and rough silver back reflector (BR) offered a quantum efficiency ($$Q_e$$

Q
e

) of 0.6031. Overall, this paper provides a full characterization of cell structure designs. It derives relationship between quantum efficiency, $$Q_e$$

Q
e

of a cell with its TCO layer’s doping methods and TCO and BR layer’s material types. Our solar cells design characterization enables us to perform a cost-benefit analysis of solar cells usage in real-world applications.
Determining the Uncertainty of Fetal Urine Production Rate Estimations
Authors: Fagerquist Mats , Carlsson Andreas , Imberg Henrik , Bokstrom Hans
Published: May 2021

The fetal urinary bladder can be observed by ultrasound and the increasing bladder volume during a filling phase is assumed to reveal the urine production. Volumes, estimated at different time points within the filling phase, allow the hourly fetal urine production rate (HFUPR) to be estimated. HFUPR estimations may add to the knowledge of fetal reactions during obstetrical complications. However, it is essential to know the degree of measurement uncertainty. Otherwise, small deviations may be overrated when repeating HFUPR estimations. The purpose of the current paper was to introduce an interactive program for calculation of HFUPR and the related standard deviation (SD). Furthermore the aim was to evaluate factors which may influence the SD of HFUPR estimations. Using the office software Excel, an interactive program was created and the application was illustrated by the filling phases of 16 fetuses. This material also enabled different realistic sets of estimation data to be simulated. Thus, SDs were calculated based on various numbers of documented bladder images and investigation times. When three instead of two bladder images were used for HFUPR estimation, the mean of SD was reduced from 22.4 to 8.1 mL/h (p < 0.0001). When the time from the first to the last measurement expanded from 10 to 30 min and four bladder images were used, the mean of SD was reduced from 7.5 to 2.4 mL/h. (p < 0.0001). An interactive program for calculation of HFUPR and the related SD was provided. Reductions in the SD with increasing number of bladder measurements and time span between measurements were demonstrated.
Effects of Dietary Palygorskite Supplementation on Cecal Microbial Community Structure and the Abundance of Antibiotic-Resistant Genes in Broiler Chickens Fed With Chlortetracycline
Authors: Jin Rui , Chen Yueping , Kang Yuru , Gu Yunfeng , Wen Chao , Wang Aiqin , Zhou Yanmin
Published: May 2021

Antibiotic-resistant genes (ARGs) have been regarded as emerging contaminants that threaten public health worldwide. Poultry excreta, often used as a fertilizer in agriculture, are a major route for the proliferation and dissemination of ARGs in the environment. The aim of the present study was to assess the potential of dietary palygorskite (Plg) supplementation as nutritional manipulation for the modulation of microbial community structure and the attenuation of ARGs in the cecal contents of broilers fed with chlortetracycline (CTC). In total, 256 one-day-old, mixed-sex, broiler chicks were allocated randomly into a 2 × 2 factorial design of four treatments, which consisted of two levels of CTC (0 or 50 mg/kg) and Plg (0 or 10 g/kg). By employing in vivo feeding and slaughter experiments, after collecting the cecal contents and extracting the total genomic DNA, 16S rRNA V3-V4 hypervariable amplicon pyrosequencing and quantitative PCR-based approaches were used to address the impact of Plg on microbiota and the abundance of ARGs in broilers. The results showed that broilers given a diet supplemented with Plg had greater α-diversity indices including Chao1, phylogenetic diversity tree, and observed-species index calculations, when compared with those without Plg supplementation. Birds given a diet supplemented with Plg had fewer Firmicutes at the phylum level, but a greater abundance of Alistipes at the bacterial genus level. Dietary Plg counteracted the CTC-induced increased abundance of ARGs, among which tet(K) had a pronounced decrease, along with a similar decreased tendency for other measured ARGs and intI1. Overall, the results indicated that Plg supplementation caused pronounced changes in cecal microbial diversity and microbiota community composition of broilers, and effectively reduced ARGs, indicating that Plg supplementation is a potential alternative measure for the attenuation of ARGs in the cecal contents of broilers.
Philippa Foot's Metaethics
Authors: Hacker-Wright John
Published: May 2021

This Element presents an interpretation and defence of Philippa Foot's ethical naturalism. It begins with the often neglected grammatical method that Foot derives from an interpretation of Ludwig Wittgenstein's later philosophy. This method shapes her approach to understanding goodness as well as the role that she attributes to human nature in ethical judgment. Moral virtues understood as perfections of human powers are central to Foot's account of ethical judgment. The thrust of the interpretation offered here is that Foot's metaethics takes ethical judgment to be tied to our self-understanding as a sort of rational animal. Foot's metaethics thereby offers a compelling contemporary approach that preserves some of the best insights of the Aristotelian tradition in practical philosophy.
Searching for a New Kenya
Authors: Diepeveen Stephanie
Published: May 2021

Searching for a New Kenya analyses public discussion in urban Kenya, focusing on the gatherings of citizens, both in-person and online, where people discuss issues of common concern to shed light on the role public discussion plays in politics and how social media affects political movements. Through rich ethnographic study of politics on the ground and online in Mombasa, Stephanie Diepeveen brings a fresh perspective on the wider challenges and dynamics of negotiating political narratives across protracted historical debates and changing digital media. Based on a critical revision of Hannah Arendt's ideas about action and power, this study explores the different dynamics of public talk in practice. It contributes to wider debates about the place and limitations of the Western canon in relation to the study of politics elsewhere, while also offering a nuanced view of why and how certain terms of debate persist in Kenya, and where the potential for change lies for public talk across changing media.
Estimate, existence and nonexistence of positive solutions of Hardy–Hénon equations
Authors: Cheng Xiyou , Wei Lei , Zhang Yimin
Published: May 2021

We consider the boundary Hardy–Hénon equation
\[ -\Delta u=(1-|x|)^{\alpha} u^{p},\ \ x\in B_1(0), \]
where $B_1(0)\subset \mathbb {R}^{N}$$(N\geq 3)$ is a ball of radial $1$ centred at $0$, $p>0$ and $\alpha \in \mathbb {R}$. We are concerned with the estimate, existence and nonexistence of positive solutions of the equation, in particular, the equation with Dirichlet boundary condition. For the case $0< p<({N+2})/({N-2})$, we establish the estimate of positive solutions. When $\alpha \leq -2$ and $p>1$, we give some conclusions with respect to nonexistence. When $\alpha >-2$ and $1< p<({N+2})/({N-2})$, we obtain the existence of positive solution for the corresponding Dirichlet problem. When $0< p\leq 1$ and $\alpha \leq -2$, we show the nonexistence of positive solutions. When $0< p<1$, $\alpha >-2$, we give some results with respect to existence and uniqueness of positive solutions.
TRAGIC NOISE AND RHETORICAL FRIGIDITY IN LYCOPHRON'SALEXANDRA
Authors: Nelson Thomas J. , Molesworth Katherine
Published: May 2021

This paper seeks to shed fresh light on the aesthetic and stylistic affiliations of Lycophron'sAlexandra, approaching the poem from two distinct but complementary angles. First, it explores what can be gained by reading Lycophron's poem against the backdrop of Callimachus’ poetry. It contends that theAlexandrapresents a radical and polemical departure from the Alexandrian's poetic programme, pointedly appropriating key Callimachean images while also countering Callimachus’ apparent dismissal of the ‘noisy’ tragic genre. Previous scholarship has noted links between the openings of theAetiaand of theAlexandra, but this article demonstrates that this relationship is only one part of a larger aesthetic divide between the two poets: by embracing the raucous acoustics of tragedy, Lycophron's poem offers a self-conscious and agonistic departure from Callimachus’ aesthetic preferences. Second, this article considers another way of conceiving the aesthetics of the poem beyond a Callimachean frame, highlighting how Lycophron pointedly engages with and evokes earlier Aristotelian literary criticism concerning the ‘frigid’ style: theAlexandraconstructs its own independent literary history centred around the alleged name of its author, ‘Lycophron’. The article proposes that this traditional attribution is best understood as a pen name that signposts the poem's stylistic affiliations, aligning it not so much with the Ptolemaic playwright Lycophron of Chalcis but rather with Lycophron the sophist and a larger rhetorical tradition of stylistic frigidity. Ultimately, through these two approaches, the article highlights further aspects of theAlexandra's aesthetic diversity.
Conflict antiquities’ rescue or ransom: The cost of buying back stolen cultural property in contexts of political violence
Authors: Hardy Samuel Andrew
Published: May 2021

Rescue has long been a defense for the removal of cultural property. Since the explosion of iconoclasm in West Asia, North Africa, and West Africa, there has been a growing demand for cultural property in danger zones to be “rescued” by being purchased and given “asylum” in “safe zones” (typically, in the market countries of Western Europe and North America). This article reviews evidence from natural experiments with the “rescue” of looted antiquities and stolen artifacts from across Asia and Europe. Unsurprisingly, the evidence reaffirms that “rescue” incentivizes looting, smuggling, and corruption, as well as forgery, and the accompanying destruction of knowledge. More significantly, “rescue” facilitates the laundering of “ordinary” illicit assets and may contribute to revenue streams of criminal organizations and violent political organizations; it may even weaken international support for insecure democracies. Ultimately, “rescue” by purchase appears incoherent, counter-productive, and dangerous for the victimized communities that it purports to support.
Finding symmetry? Archaeology, Objects, and Posthumanism
Authors: Witmore Christopher
Published: May 2021

Well before the turn of the century, it had become clear that archaeology's aspiration to study the past was, true to the modern project, a pretext for a deeper desire to fabricate its objects. Material culture, materiality, the material past, material residues, heritage—the objects of interpretive (post-processual) archaeology could only be characterized as a continuation of this modern project. While finding symmetry was tied to an upheaval from this mode of disciplinary production, it may now be characterized as one cue among others in more agile archaeological theory. After briefly contrasting archaeological thought before and after the turn of the century, this article sketches out some of the core features of an object-oriented approach to things, including symmetry, irreduction, emergent causality, and strangeness, among others. It then outlines how, by finding our way alongside things, we might aspire to ever more creative work with archaeological objects and their pasts. Finally, it closes with a few words on Posthumanism.
Combining the Theory and Practice of Peace and Conflict Studies through an Experiential Conflict Analysis Activity
Authors: Blewitt Amanda , Choi Christine , King Elisabeth
Published: May 2021

How can political science classes best prepare undergraduate students for the field of peace and conflict studies (PACS)? We argue that well-designed experiential learning activities provide opportunities for students to embrace complexity and practice adaptability, fusing the theoretical and practical in ways that prepare them to engage in PACS. This article presents one such experiential learning approach: a conflict analysis activity. Through engaging in a messy learning process, students (1) gain an increased theoretical understanding of the complexity of conflict, (2) practice adaptability, and (3) increase their self-efficacy. We provide a step-by-step description of the Conflict Analysis Tool exercise and reflect on how well the activity enables the use of knowledge and skills relevant for PACS. Our goal is that the insights gained through our approach will be helpful to other educators—from PACS to international relations to American politics and beyond.
Analysis of Suicides Reported as Adverse Events in Psychiatry Resulted in Nine Quality Improvement Initiatives
Authors: Mackenhauer Julie , Winsløv Jan-Henrik , Holmskov Jens , Brødsgaard Inger , Larsen Tina Gram , Mainz Jan
Published: May 2021

Abstract. Background: The majority of persons who die by suicide have a mental disorder. Preventive strategies should include addressing social and psychological factors and the treatment of the mental disorder. Aim: We aimed to identify breaches in clinical care and identify areas for quality improvement initiatives. Method: An aggregate analysis of suicides reported as adverse events during 2012–2016 to Psychiatry, North Denmark Region was carried out. We developed an audit chart and identified items through (a) medical chart review and (b) consensus meetings in an expert panel. Results: A total of 35 cases were analyzed. Suicide risk assessments were adequately documented in the medial chart in six of 35 cases. Risk assessments emphasized suicidal ideation rather than well-known risk factors such as previous suicide attempts, substance abuse, physical illness, or job loss. Relatives were involved in four of 35 of the risk assessments. The panel suggested nine areas for quality improvement. Limitations: Most people who die by suicide are not seen in mental health facilities prior to suicide, and hence conclusions can only be generalized to these patients. Information on the gap between “Work-as-Done” and “Work-As-Imagined” was not recognized. Conclusion: Most of the risk assessments among suicides reported as adverse events to our mental health facilities were insufficient. Quality improvement initiatives focusing on training, documentation, involving relatives, communication, and data sharing must be planned to improve clinical care.
Railway Suicide in The Netherlands Lower Than Expected
Authors: van Houwelingen Cornelis A. J. , Di Bucchianico Alessandro , Beersma Domien G. M. , Kerkhof Ad J. F. M.
Published: May 2021

Abstract. Background: Increasing rail transportation requires appropriate railway suicide preventive measures. Aims: The investigation of trends in railway suicide during 2008–2018, a period in which preventive measures were taken by Dutch railway infrastructure manager ProRail. Methods: Generalized linear regression models for railway suicide were developed for the period 1970–2007 with general suicide rate, railway traffic intensity, and a combination of these variables as regressors. Subsequently, the best-fitting model was used to investigate trends in railway suicide after 2007 by comparing in retrospect observed values with the expected outcomes of the regression model. Results: An adequate regression model for railway suicide was obtained using both general suicide rate and railway traffic intensity as regressors. Based on this model, while national suicide mortality and railway traffic increased, a distinct relative decline in railway suicides was found from 2012 onward. Conclusions: This decline of railway suicides in the Netherlands may indicate that preventive measures taken by ProRail were effective and prevented around 85 railway suicides annually, a reduction of 30%.
Spatial Distributions of At‐Many‐Stations Hydraulic Geometry for Mountain Rivers Originated From the Qinghai‐Tibet Plateau
Authors: Qin Chao , Wu Baosheng , Wang Guangqian , Wang Ge
Published: May 2021

At‐many‐stations hydraulic geometry (AMHG) has provided a novel way to understand river network development, simulate water flow, and retrieve river discharge in data‐scared regions. Based on in‐situ measurements of six major rivers originating from the Qinghai‐Tibet Plateau (QTP), this study verifies the existence of AMHG relations along the rivers and explores AMHG relations for cross sections that are not located in the same river reach. The mainstreams and tributaries of the studied rivers in the southern and the eastern portions of the QTP have satisfactory AMHG relation strengths with R2 > 0.9 for over 60% of the relations. For cross sections located in the same stream order or within a certain range of contributing area (CA), approximately 60% (9/15) and 53% (8/15) of the AMHG relations have an R2 > 0.6. AMHG strength increases with increasing stream order and CA; this finding reflects the increasing coherence and maturity of the river networks associated with the geomorphic shaping power of increased discharge. Width‐AMHG intercepts are larger than those of depth‐AMHG and velocity‐AMHG for all stream orders and CAs. Most of the congruent hydraulics generated from cross sections located in middle‐scale rivers (orders 7–8) are within the observed range. Congruent hydraulics generally increase with an increase in in‐situ measured hydraulics when the stream order or the CA increases. The AMHG relations existing among cross sections that are not located in the same reach, which is named as cross channel AMHG, indicate linear variability of cross‐sectional geometric and hydraulic similarities in the same stream order or within a certain CA range. The results break the watershed divide boundary control on AMHG and have the potential to provide background knowledge for discharge estimation in mountain rivers located in the QTP.
Susan L. Beck Receives 2020 Walter H. Bucher Medal
Authors:   AGU
Published: May 2021

Susan L. Beck was awarded the 2020 Walter H. Bucher Medal at the virtual AGU Fall Meeting in December. The medal is for “original contributions to the basic knowledge of the crust and lithosphere.”
First Comparison of Traveling Atmospheric Disturbances Observed in the Middle Thermosphere by Global‐Scale Observations of the Limb and Disk to Traveling Ionospheric Disturbances Seen in Ground‐Based Total Electron Content Observations
Authors: England Scott L. , Greer Katelynn R. , Zhang Shun‐Rong , Evans Scott , Solomon Stanley C. , Eastes Richard W. , McClintock William E. , Burns Alan G.
Published: May 2021

Traveling ionospheric disturbances (TIDs) and their neutral counterparts known as traveling atmospheric disturbances (TADs) are believed to play a role in communicating inputs to other locations in the fluid. While these two phenomena are believed to be connected, they may not have a one‐to‐one correspondence as the geomagnetic field influences the TID but has no direct impact on the TAD. The relative amplitudes of the perturbations seen in the ionosphere and atmosphere have been observed but rarely together. This study reports results from a 3‐day campaign to observe TIDs and TADs simultaneously over a broad latitudinal region over the eastern United States using a combination of Global‐scale Observations of the Limb and Disk (GOLD) and a distributed network of ground‐based Global Navigation Satellite System (GNSS) receivers. These results demonstrate that GOLD and the ground‐based total electron content (TEC) observations can see the atmospheric and ionospheric portions of a large‐scale traveling disturbance. The phase difference in the perturbations to the GOLD airglow brightness, O/N2 and thermospheric disk temperature are consistent with an atmospheric gravity wave moving through this region. The ionospheric signatures move at the same rate as those in the atmosphere, but their amplitudes do not have a simple correspondence to the amplitude of the signal seen in the atmosphere. This campaign demonstrates a proof‐of‐concept that this combination of observations is able to provide information on TIDs and TADs, including quantifying their impact on the temperature and chemical composition of the upper atmosphere.
Proximity to Undersaturation and the Influences on G. bulloides Area‐Density in Southern Indian Ocean Marine Sediments
Authors: Umling N. E. , Saad B. , Sikes E. , Goodkin N. F.
Published: May 2021

The area density proxy of foraminiferal shell thickness and calcification intensity has the potential to provide information about past ocean CO2 content and has the benefit of small sample requirements, simple analytical techniques, and the ability to re‐use the analyzed foraminifera for other paleo‐proxies. Using a series of multicore core‐tops collected from the southeastern Indian Ocean (1.8–3.8 km water depth), we evaluate the reliability of utilizing area density values of Globigerina bulloides from sediment cores to estimate surface ocean carbonate parameters. Because foraminifera in marine sediments can rarely be considered “pristine” (or “glassy”), we grouped area density measurements of shells to designate various stages of diagenesis. Visual signs of alteration were apparent at area density values as low as ∼0.122 × 104 µg/µm2, with deviations from the “pristine” endmember beginning at area density values of ∼0.087 × 104 µg/µm2. We find that increases in area density overprint the surface ocean carbonate signature in thicker (>0.122 × 104 µg/µm2 shells), but small increases associated with marine sedimentary burial and diagenesis can be accounted for, allowing this proxy to be applied back in time. Reconstructing the distribution of area density values in a given sample has the potential to provide valuable information on overall sample preservation by estimating the percent of well‐preserved shells (<0.122 × 104 µg/µm2; %wp) in a given sample. Our %wp metric has the potential for use as a proxy for lysocline variability in addition to assessing the suitability of marine sediment samples for surface ocean reconstructions.
UBQLN1 mediates sorafenib resistance through regulating mitochondrial biogenesis and ROS homeostasis by targeting PGC1β in hepatocellular carcinoma
Authors: Xu Junjie , Ji Lin , Ruan Yeling , Wan Zhe , Lin Zhongjie , Xia Shunjie , Tao Liye , Zheng Junhao , Cai Liuxin , Wang Yifan , Liang Xiao , Cai Xiujun
Published: May 2021

The treatment for hepatocellular carcinoma (HCC) is promising in recent years, but still facing critical challenges. The first targeted therapy, sorafenib, prolonged the overall survival by months. However, resistance often occurs, largely limits its efficacy. Sorafenib was found to target the electron transport chain complexes, which results in the generation of reactive oxygen species (ROS). To maintain sorafenib resistance and further facilitate tumor progression, cancer cells develop strategies to overcome excessive ROS production and obtain resistance to oxidative stress-induced cell death. In the present study, we investigated the roles of ROS in sorafenib resistance, and found suppressed ROS levels and reductive redox states in sorafenib-resistant HCC cells. Mitochondria in sorafenib-resistant cells maintained greater functional and morphological integrity under the treatment of sorafenib. However, cellular oxygen consumption rate and mitochondria DNA content analyses revealed fewer numbers of mitochondria in sorafenib-resistant cells. Further investigation attributed this finding to decreased mitochondrial biogenesis, likely caused by the accelerated degradation of peroxisome proliferator-activated receptor γ coactivator 1β (PGC1β). Mechanistic dissection showed that upregulated UBQLN1 induced PGC1β degradation in a ubiquitination-independent manner to attenuate mitochondrial biogenesis and ROS production in sorafenib-resistant cells under sorafenib treatment. Furthermore, clinical investigations further indicated that the patients with higher UBQLN1 levels experienced worse recurrence-free survival. In conclusion, we propose a novel mechanism involving mitochondrial biogenesis and ROS homeostasis in sorafenib resistance, which may offer new therapeutic targets and strategies for HCC patients.
Genomic evolution of the class Acidithiobacillia: deep-branching Proteobacteria living in extreme acidic conditions
Authors: Moya-Beltrán Ana , Beard Simón , Rojas-Villalobos Camila , Issotta Francisco , Gallardo Yasna , Ulloa Ricardo , Giaveno Alejandra , Degli Esposti Mauro , Johnson D Barrie , Quatrini Raquel
Published: May 2021

Members of the genus Acidithiobacillus, now ranked within the class Acidithiobacillia, are model bacteria for the study of chemolithotrophic energy conversion under extreme conditions. Knowledge of the genomic and taxonomic diversity of Acidithiobacillia is still limited. Here, we present a systematic analysis of nearly 100 genomes from the class sampled from a wide range of habitats. Some of these genomes are new and others have been reclassified on the basis of advanced genomic analysis, thus defining 19 Acidithiobacillia lineages ranking at different taxonomic levels. This work provides the most comprehensive classification and pangenomic analysis of this deep-branching class of Proteobacteria to date. The phylogenomic framework obtained illuminates not only the evolutionary past of this lineage, but also the molecular evolution of relevant aerobic respiratory proteins, namely the cytochrome bo3 ubiquinol oxidases.
LncRNA CD27-AS1 promotes acute myeloid leukemia progression through the miR-224-5p/PBX3 signaling circuit
Authors: Tao Yanling , Zhang Jingjing , Chen Lulu , Liu Xin , Yao Mingkang , Zhang Hao
Published: May 2021

Acute myeloid leukemia (AML) is a hematological malignancy with a low cure rate, especially in the elderly. Previous studies have shown that long non-coding RNA (lncRNA) may be an important factor in the pathogenesis of hematological malignancies, including acute myeloid leukemia (AML). However, the biological roles and clinical significances of most lncRNAs in AML are not fully understood. LncRNA CD27 Antisense RNA 1 (CD27-AS1), as a member of lncRNA family, has rare reports on its function. In present study, we found that the expression of CD27-AS1 examined by quantitative real-time PCR was markedly increased in the AML patients (N = 40) compared with healthy volunteers (N = 40). The overall survival time was significantly shorter in patients with higher CD27-AS1 expression than that in patients with lower CD27-AS1 (P < 0.01). Furthermore, downregulation of CD27-AS1 in AML cells suppressed proliferative ability, arrested cell cycle in G0/G1 phase, and induced apoptosis. However, CD27-AS1 overexpression further enhanced the malignant phenotype of AML cells. Additionally, CD27-AS1 was proved to increase PBX3 expression through sponging miR-224-5p. CD27-AS1 knockdown blocked the MAPK signaling through PBX3 silencing and further inhibited the cell growth of AML cells. Taken together, we demonstrate that CD27-AS1 may be a potential prognostic biomarker of AML, and our finding also provides a new insight for non-coding RNA-based therapeutic intervention of AML.
Gene-level metagenomic architectures across diseases yield high-resolution microbiome diagnostic indicators
Authors: Tierney Braden T. , Tan Yingxuan , Kostic Aleksandar D. , Patel Chirag J.
Published: May 2021

We propose microbiome disease “architectures”: linking >1 million microbial features (species, pathways, and genes) to 7 host phenotypes from 13 cohorts using a pipeline designed to identify associations that are robust to analytical model choice. Here, we quantify conservation and heterogeneity in microbiome-disease associations, using gene-level analysis to identify strain-specific, cross-disease, positive and negative associations. We find coronary artery disease, inflammatory bowel diseases, and liver cirrhosis to share gene-level signatures ascribed to the Streptococcus genus. Type 2 diabetes, by comparison, has a distinct metagenomic signature not linked to any one specific species or genus. We additionally find that at the species-level, the prior-reported connection between Solobacterium moorei and colorectal cancer is not consistently identified across models—however, our gene-level analysis unveils a group of robust, strain-specific gene associations. Finally, we validate our findings regarding colorectal cancer and inflammatory bowel diseases in independent cohorts and identify that features inversely associated with disease tend to be less reproducible than features enriched in disease. Overall, our work is not only a step towards gene-based, cross-disease microbiome diagnostic indicators, but it also illuminates the nuances of the genetic architecture of the human microbiome, including tension between gene- and species-level associations.
The genetic architecture of the human thalamus and its overlap with ten common brain disorders
Authors: Elvsåshagen Torbjørn , Shadrin Alexey , Frei Oleksandr , van der Meer Dennis , Bahrami Shahram , Kumar Vinod Jangir , Smeland Olav , Westlye Lars T. , Andreassen Ole A. , Kaufmann Tobias
Published: May 2021

The thalamus is a vital communication hub in the center of the brain and consists of distinct nuclei critical for consciousness and higher-order cortical functions. Structural and functional thalamic alterations are involved in the pathogenesis of common brain disorders, yet the genetic architecture of the thalamus remains largely unknown. Here, using brain scans and genotype data from 30,114 individuals, we identify 55 lead single nucleotide polymorphisms (SNPs) within 42 genetic loci and 391 genes associated with volumes of the thalamus and its nuclei. In an independent validation sample (n = 5173) 53 out of the 55 lead SNPs of the discovery sample show the same effect direction (sign test,P = 8.6e-14). We map the genetic relationship between thalamic nuclei and 180 cerebral cortical areas and find overlapping genetic architectures consistent with thalamocortical connectivity. Pleiotropy analyses between thalamic volumes and ten psychiatric and neurological disorders reveal shared variants for all disorders. Together, these analyses identify genetic loci linked to thalamic nuclei and substantiate the emerging view of the thalamus having central roles in cortical functioning and common brain disorders.
Self-clocking fast and variation tolerant true random number generator based on a stochastic mott memristor
Authors: Kim Gwangmin , In Jae Hyun , Kim Young Seok , Rhee Hakseung , Park Woojoon , Song Hanchan , Park Juseong , Kim Kyung Min
Published: May 2021

The intrinsic stochasticity of the memristor can be used to generate true random numbers, essential for non-decryptable hardware-based security devices. Here, we propose a novel and advanced method to generate true random numbers utilizing the stochastic oscillation behavior of a NbOx mott memristor, exhibiting self-clocking, fast and variation tolerant characteristics. The random number generation rate of the device can be at least 40 kb s−1, which is the fastest record compared with previous volatile memristor-based TRNG devices. Also, its dimensionless operating principle provides high tolerance against both ambient temperature variation and device-to-device variation, enabling robust security hardware applicable in harsh environments.
Semiconducting polymer nano-PROTACs for activatable photo-immunometabolic cancer therapy
Authors: Zhang Chi , Zeng Ziling , Cui Dong , He Shasha , Jiang Yuyan , Li Jingchao , Huang Jiaguo , Pu Kanyi
Published: May 2021

Immunometabolic intervention has been applied to treat cancer via inhibition of certain enzymes associated with intratumoral metabolism. However, small-molecule inhibitors and genetic modification often suffer from insufficiency and off-target side effects. Proteolysis targeting chimeras (PROTACs) provide an alternative way to modulate protein homeostasis for cancer therapy; however, the always-on bioactivity of existing PROTACs potentially leads to uncontrollable protein degradation at non-target sites, limiting their in vivo therapeutic efficacy. We herein report a semiconducting polymer nano-PROTAC (SPNpro) with phototherapeutic and activatable protein degradation abilities for photo-immunometabolic cancer therapy. SPNpro can remotely generate singlet oxygen (1O2) under NIR photoirradiation to eradicate tumor cells and induce immunogenic cell death (ICD) to enhance tumor immunogenicity. Moreover, the PROTAC function of SPNpro is specifically activated by a cancer biomarker (cathepsin B) to trigger targeted proteolysis of immunosuppressive indoleamine 2,3-dioxygenase (IDO) in the tumor of living mice. The persistent IDO degradation blocks tryptophan (Trp)-catabolism program and promotes the activation of effector T cells. Such a SPNpro-mediated in-situ immunometabolic intervention synergizes immunogenic phototherapy to boost the antitumor T-cell immunity, effectively inhibiting tumor growth and metastasis. Thus, this study provides a polymer platform to advance PROTAC in cancer therapy.
Phospholipid translocation captured in a bifunctional membrane protein MprF
Authors: Song Danfeng , Jiao Haizhan , Liu Zhenfeng
Published: May 2021

As a large family of membrane proteins crucial for bacterial physiology and virulence, the Multiple Peptide Resistance Factors (MprFs) utilize two separate domains to synthesize and translocate aminoacyl phospholipids to the outer leaflets of bacterial membranes. The function of MprFs enablesStaphylococcus aureusand other pathogenic bacteria to acquire resistance to daptomycin and cationic antimicrobial peptides. Here we present cryo-electron microscopy structures of MprF homodimer fromRhizobium tropici(RtMprF) at two different states in complex with lysyl-phosphatidylglycerol (LysPG).RtMprF contains a membrane-embedded lipid-flippase domain with two deep cavities opening toward the inner and outer leaflets of the membrane respectively. Intriguingly, a hook-shaped LysPG molecule is trapped inside the inner cavity with its head group bent toward the outer cavity which hosts a second phospholipid-binding site. Moreover,RtMprF exhibits multiple conformational states with the synthase domain adopting distinct positions relative to the flippase domain. Our results provide a detailed framework for understanding the mechanisms of MprF-mediated modification and translocation of phospholipids.
Cortical and subcortical signatures of conscious object recognition
Authors: Levinson Max , Podvalny Ella , Baete Steven H. , He Biyu J.
Published: May 2021

The neural mechanisms underlying conscious recognition remain unclear, particularly the roles played by the prefrontal cortex, deactivated brain areas and subcortical regions. We investigated neural activity during conscious object recognition using 7 Tesla fMRI while human participants viewed object images presented at liminal contrasts. Here, we show both recognized and unrecognized images recruit widely distributed cortical and subcortical regions; however, recognized images elicit enhanced activation of visual, frontoparietal, and subcortical networks and stronger deactivation of the default-mode network. For recognized images, object category information can be decoded from all of the involved cortical networks but not from subcortical regions. Phase-scrambled images trigger strong involvement of inferior frontal junction, anterior cingulate cortex and default-mode network, implicating these regions in inferential processing under increased uncertainty. Our results indicate that content-specific activity in both activated and deactivated cortical networks and non-content-specific subcortical activity support conscious recognition.
Circulating amino acids and amino acid-related metabolites and risk of breast cancer among predominantly premenopausal women
Authors: Zeleznik Oana A. , Balasubramanian Raji , Zhao Yibai , Frueh Lisa , Jeanfavre Sarah , Avila-Pacheco Julian , Clish Clary B. , Tworoger Shelley S. , Eliassen A. Heather
Published: May 2021

Known modifiable risk factors account for a small fraction of premenopausal breast cancers. We investigated associations between pre-diagnostic circulating amino acid and amino acid-related metabolites (N = 207) and risk of breast cancer among predominantly premenopausal women of the Nurses’ Health Study II using conditional logistic regression (1057 cases, 1057 controls) and multivariable analyses evaluating all metabolites jointly. Eleven metabolites were associated with breast cancer risk (q-value < 0.2). Seven metabolites remained associated after adjustment for established risk factors (p-value < 0.05) and were selected by at least one multivariable modeling approach: higher levels of 2-aminohippuric acid, kynurenic acid, piperine (all three with q-value < 0.2), DMGV and phenylacetylglutamine were associated with lower breast cancer risk (e.g., piperine: ORadjusted (95%CI) = 0.84 (0.77–0.92)) while higher levels of creatine and C40:7 phosphatidylethanolamine (PE) plasmalogen were associated with increased breast cancer risk (e.g., C40:7 PE plasmalogen: ORadjusted (95%CI) = 1.11 (1.01–1.22)). Five amino acids and amino acid-related metabolites (2-aminohippuric acid, DMGV, kynurenic acid, phenylacetylglutamine, and piperine) were inversely associated, while one amino acid and a phospholipid (creatine and C40:7 PE plasmalogen) were positively associated with breast cancer risk among predominately premenopausal women, independent of established breast cancer risk factors.
Rabbit as an animal model for the study of biological grafts in pelvic floor dysfunctions
Authors: Peró Marta , Casani Laura , Castells-Sala Cristina , Pérez Maria Luisa , Moga Naranjo Esther , Juan-Babot Oriol , Alserawan De Lamo Leticia , López-Chicón Patricia , Vilarrodona Serrat Anna , Badimon Lina , Porta Roda Oriol
Published: May 2021

The aims of this study were to evaluate the feasibility of the New Zealand White (NZW) rabbit for studying implanted biomaterials in pelvic reconstructive surgery; and to compare the occurrence of graft-related complications of a commercial polypropylene (PP) mesh and new developed human dermal matrix implanted at vaginal and abdominal level. 20 white female NZW rabbits were randomized into two groups, experimental group (human acellular dermal matrices-hADM-graft) and control group (commercial PP graft). In each animal, grafts were surgically implanted subcutaneously in the abdominal wall and in the vaginal submucosa layer for 180 days. The graft segments were then removed and the surgical and clinical results were analyzed. The main surgical challenges during graft implantation were: (a) an adequate vaginal exposure while maintaining the integrity of the vaginal mucosa layer; (b) to keep aseptic conditions; (c) to locate and dissect the breast vein abdominal surgery; and (d) to withdraw blood samples from the ear artery. The most abnormal findings during the explant surgery were found in the PP group (33% of vaginal mesh extrusion) in comparison with the hADM group (0% of vaginal graft extrusion), p = 0.015. Interestingly, macroscopic observation showed that the integration of the vaginal grafts was more common in the hADM group (40%) than in the PP group, in which the vaginal mesh was identified in 100% of the animals (p = 0.014). The NZW rabbit is a good model for assessing materials to be used as grafts for pelvic reconstructive surgery and vaginal surgery. Animals are easily managed during the procedures, including surgical intervention and vaginal mucosa approach. Additionally, hADM is associated with fewer clinical complications, as well as better macroscopic tissue integration, compared to PP mesh.
Machine learning based differentiation of glioblastoma from brain metastasis using MRI derived radiomics
Authors: Priya Sarv , Liu Yanan , Ward Caitlin , Le Nam H. , Soni Neetu , Pillenahalli Maheshwarappa Ravishankar , Monga Varun , Zhang Honghai , Sonka Milan , Bathla Girish
Published: May 2021

Few studies have addressed radiomics based differentiation of Glioblastoma (GBM) and intracranial metastatic disease (IMD). However, the effect of different tumor masks, comparison of single versus multiparametric MRI (mp-MRI) or select combination of sequences remains undefined. We cross-compared multiple radiomics based machine learning (ML) models using mp-MRI to determine optimized configurations. Our retrospective study included 60 GBM and 60 IMD patients. Forty-five combinations of ML models and feature reduction strategies were assessed for features extracted from whole tumor and edema masks using mp-MRI [T1W, T2W, T1-contrast enhanced (T1-CE), ADC, FLAIR], individual MRI sequences and combined T1-CE and FLAIR sequences. Model performance was assessed using receiver operating characteristic curve. For mp-MRI, the best model was LASSO model fit using full feature set (AUC 0.953). FLAIR was the best individual sequence (LASSO-full feature set, AUC 0.951). For combined T1-CE/FLAIR sequence, adaBoost-full feature set was the best performer (AUC 0.951). No significant difference was seen between top models across all scenarios, including models using FLAIR only, mp-MRI and combined T1-CE/FLAIR sequence. Top features were extracted from both the whole tumor and edema masks. Shape sphericity is an important discriminating feature.