bluuebunny/crossref_metadata_2025 huggingface dataset:
Otorhinolaryngological manifestations of coronavirus disease 2019: a prospective review of 600 patients
Authors: Bhatta S , Gandhi S , Saindani S J , Ganesuni D , Ghanpur A D
Published: January 2021

Objectives

To evaluate otorhinolaryngological manifestations of coronavirus disease 2019 infection and the time required for their resolution.

Methods

A prospective analysis was conducted of coronavirus disease 2019 patients presenting from 1 April 2020 to 30 July 2020. The otorhinolaryngological manifestations were evaluated based on patient history. The time required for symptom resolution was evaluated separately for intensive care unit and non-intensive care unit patients.

Results

A total of 600 patients were included in the study; 13.3 per cent required the intensive care unit and 2.2 per cent expired. The otorhinolaryngological manifestations were: sore throat (88 per cent), fever (78.8 per cent), anosmia or hyposmia (63.6 per cent), ageusia or hypogeusia (63.5 per cent), rhinorrhoea (51.3 per cent), nasal obstruction (33.5 per cent), sneezing (30.3 per cent), and breathing difficulty (18.6 per cent). The time required for symptom resolution was longest for breathing difficulty (23.6 days for intensive care unit and 8.2 days for non-intensive care unit patients).

Conclusion

Otorhinolaryngological symptoms are one of the main presentations of coronavirus disease 2019 infection. The increased prevalence of medical co-morbidities in patients requiring intensive care unit and in deceased patients is also highlighted.
Dynamic networks of psychotic symptoms in adults living in precarious housing or homelessness
Authors: Jones Andrea A. , Gicas Kristina M. , Mostafavi Sara , Woodward Melissa L. , Leonova Olga , Vila-Rodriguez Fidel , Procyshyn Ric M. , Cheng Alex , Buchanan Tari , Lang Donna J. , MacEwan G. William , Panenka William J. , Barr Alasdair M. , Thornton Allen E. , Honer William G.
Published: January 2021

Background

People living in precarious housing or homelessness have higher than expected rates of psychotic disorders, persistent psychotic symptoms, and premature mortality. Psychotic symptoms can be modeled as a complex dynamic system, allowing assessment of roles for risk factors in symptom development, persistence, and contribution to premature mortality.

Method

The severity of delusions, conceptual disorganization, hallucinations, suspiciousness, and unusual thought content was rated monthly over 5 years in a community sample of precariously housed/homeless adults (n = 375) in Vancouver, Canada. Multilevel vector auto-regression analysis was used to construct temporal, contemporaneous, and between-person symptom networks. Network measures were compared between participants with (n = 219) or without (n = 156) history of psychotic disorder using bootstrap and permutation analyses. Relationships between network connectivity and risk factors including homelessness, trauma, and substance dependence were estimated by multiple linear regression. The contribution of network measures to premature mortality was estimated by Cox proportional hazard models.

Results

Delusions and unusual thought content were central symptoms in the multilevel network. Each psychotic symptom was positively reinforcing over time, an effect most pronounced in participants with a history of psychotic disorder. Global connectivity was similar between those with and without such a history. Greater connectivity between symptoms was associated with methamphetamine dependence and past trauma exposure. Auto-regressive connectivity was associated with premature mortality in participants under age 55.

Conclusions

Past and current experiences contribute to the severity and dynamic relationships between psychotic symptoms. Interrupting the self-perpetuating severity of psychotic symptoms in a vulnerable group of people could contribute to reducing premature mortality.
Tools for interpreting Christ's saving mysteries in scripture: Aquinas on reduplicative propositions in christology
Authors: Moser J. David
Published: January 2021

This article examines how Thomas Aquinas used reduplicative propositions (e.g. ‘Christ suffersinsofar as he is a human being’) to explicate Christ's saving mysteries, or events that Christ did and suffered that produced states of affairs only God can do. Following scripture's focus on Christ as one acting subject, Aquinas argued that we should use the adverbial modifiers ‘authoritatively as God and instrumentally as a human being’ to speak well of Christ's saving mysteries as actions of a single subject. This approach is theologically beneficial because it avoids the pitfalls of thinking of Christ's natures as agents.
The representation of public values in health technology assessment to inform funding decisions: the case of Australia's national funding bodies
Authors: Haji Ali Afzali Hossein , Street Jackie , Merlin Tracy , Karnon Jonathan
Published: January 2021

Over the past few years, there has been an increasing recognition of the value of public involvement in health technology assessment (HTA) to ensure the legitimacy and fairness of public funding decisions [Street J, Stafinski T, Lopes E, Menon D. Defining the role of the public in Health Technology Assessment (HTA) and HTA-informed decision-making processes.Int J Technol Assess Health Care. 2020;36:87–95]. However, important challenges remain, in particular, how to reorient HTA to reflect public priorities. In a recent international survey of thirty HTA agencies conducted by the International Network of Agencies for HTA (INAHTA), public engagement in HTA was listed as one of the “Top 10” challenges for HTA agencies [O'Rourke B, Werko SS, Merlin T, Huang LY, Schuller T. The “Top 10” challenges for health technology assessment: INAHTA viewpoint.Int J Technol Assess. 2020;36:1–4].

Historically, Australia has been at the forefront of the application of HTA for assessing the effectiveness and cost-effectiveness of new health technologies to inform public funding decisions. However, current HTA processes in Australia lack meaningful public inputs. Using Australia as an example, we describe this important limitation and discuss the potential impact of this gap on the health system and future directions.
Influences of reopening businesses and social venues: COVID-19 incidence rate in East Texas county
Authors: Le Tuan D. , Bosworth Michele , Ledlow Gerald , Le Tony T. , Bell Jeffrey , Singh Karan P.
Published: January 2021

As the on-going severe acute respiratory syndrome coronavirus 2 pandemic, we aimed to understand whether economic reopening (EROP) significantly influenced coronavirus disease 2019 (COVID-19) incidence. COVID-19 data from Texas Health and Human Services between March and August 2020 were analysed. COVID-19 incidence rate (cases per 100 000 population) was compared to statewide for selected urban and rural counties. We used joinpoint regression analysis to identify changes in trends of COVID-19 incidence and interrupted time-series analyses for potential impact of state EROP orders on COVID-19 incidence. We found that the incidence rate increased to 145.1% (95% CI 8.4–454.5%) through 4th April, decreased by 15.5% (95% CI −24.4 −5.9%) between 5th April and 30th May, increased by 93.1% (95% CI 60.9–131.8%) between 31st May and 11th July and decreased by 13.2% (95% CI −22.2 −3.2%) after 12 July 2020. The study demonstrates the EROP policies significantly impacted trends in COVID-19 incidence rates and accounted for increases of 129.9 and 164.6 cases per 100 000 populations for the 24- or 17-week model, respectively, along with other county and state reopening ordinances. The incidence rate decreased sharply after 12th July considering the emphasis on a facemask or covering requirement in business and social settings.
The neuroscience of diabetic retinopathy
Authors: Antonetti David A.
Published: January 2021

Diabetic retinopathy remains a leading cause of blindness despite recent advance in therapies. Traditionally, this complication of diabetes was viewed predominantly as a microvascular disease but research has pointed to alterations in ganglion cells, glia, microglia, and photoreceptors as well, often occurring without obvious vascular damage. In neural tissue, the microvasculature and neural tissue form an intimate relationship with the neural tissue providing signaling cues for the vessels to form a distinct barrier that helps to maintain the proper neuronal environment for synaptic signaling. This relationship has been termed the neurovascular unit (NVU). Research is now focused on understanding the cellular and molecular basis of the neurovascular unit and how diabetes alters the normal cellular communications and disrupts the cellular environment contributing to loss of vision in diabetes.
Well-posedness of the Muskat problem in subcritical Lp-Sobolev spaces
Authors: ABELS H. , MATIOC B.-V.
Published: January 2021

We study the Muskat problem describing the vertical motion of two immiscible fluids in a two-dimensional homogeneous porous medium in an Lp-setting with p ∈ (1, ∞). The Sobolev space
$W_p^s(\mathbb R)$
with s = 1+1/p is a critical space for this problem. We prove, for each s ∈ (1+1/p, 2) that the Rayleigh–Taylor condition identifies an open subset of
$W_p^s(\mathbb R)$
within which the Muskat problem is of parabolic type. This enables us to establish the local well-posedness of the problem in all these subcritical spaces together with a parabolic smoothing property.
Impact of body mass index on intracytoplasmic sperm injection in women with polycystic ovary syndrome
Authors: Kamardi Stanly , Surya IGN Harry Wijaya , Mahendra I Nyoman Bayu , Adnyana IB Putra , Suardika Anom , Tondohusodo Nono , Sudiman Jaqueline
Published: January 2021

Polycystic ovary syndrome (PCOS) is a condition that affects fertility. There are two types of PCOS; the normal/lean type and overweight/obese type. The aim of this study was to assess baseline characteristics, ovarian response, quality of oocytes, embryos, pregnancy, implantation and live birth rates in normal/lean and overweight/obese patients with PCOS undergoing ICSI compared with patients without PCOS. This retrospective case–control analytical study included 38 normal/lean and 17 overweight/obese patients with PCOS, and 98 normal/lean and 17 overweight/obese patients without PCOS. Parameters were observed based on baseline characteristics, ovarian response to dosage and duration of gonadotropin administered, number of oocytes, matured oocytes, fertilization rate, embryo quality and development, pregnancy, implantation and live birth rates. Basal serum luteinizing hormone in normal/lean PCOS was significantly higher compared with non-PCOS groups. Total dosage of gonadotropin used was significantly lower in normal/lean PCOS compared with other groups. End estradiol levels in normal/lean PCOS was significantly higher compared with the non-PCOS groups. Number of follicles, retrieved oocytes and matured oocytes were significantly higher in PCOS groups compared with the non-PCOS groups. However, there were no differences in fertilized oocytes, cleavage, number of top-quality embryos, pregnancy, implantation, and live birth rates among groups. This present study suggests that normal/lean PCOS requires lower gonadotropin dosages and that patients with PCOS have more follicles and oocytes compared with patients without PCOS, however the number of fertilized oocytes and embryos from patients with PCOS were the same as those from patients without PCOS and suggested that the quality of retrieved oocytes in PCOS might be compromised.
Comparison of Education and Episodic Memory as Modifiers of Brain Atrophy Effects on Cognitive Decline: Implications for Measuring Cognitive Reserve
Authors: Mungas Dan , Fletcher Evan , Gavett Brandon E. , Widaman Keith , Zahodne Laura B. , Hohman Timothy J. , Mayeda Elizabeth Rose , Dowling N. Maritza , Johnson David K. , Tomaszewski Farias Sarah
Published: January 2021

Objective:

This study compared the level of education and tests from multiple cognitive domains as proxies for cognitive reserve.

Method:

The participants were educationally, ethnically, and cognitively diverse older adults enrolled in a longitudinal aging study. We examined independent and interactive effects of education, baseline cognitive scores, and MRI measures of cortical gray matter change on longitudinal cognitive change.

Results:

Baseline episodic memory was related to cognitive decline independent of brain and demographic variables and moderated (weakened) the impact of gray matter change. Education moderated (strengthened) the gray matter change effect. Non-memory cognitive measures did not incrementally explain cognitive decline or moderate gray matter change effects.

Conclusions:

Episodic memory showed strong construct validity as a measure of cognitive reserve. Education effects on cognitive decline were dependent upon the rate of atrophy, indicating education effectively measures cognitive reserve only when atrophy rate is low. Results indicate that episodic memory has clinical utility as a predictor of future cognitive decline and better represents the neural basis of cognitive reserve than other cognitive abilities or static proxies like education.
Impact of sugar-sweetened beverage taxes on price, import and sale volumes in an island: interrupted time series analysis
Authors: Teng Andrea M , Genç Murat , Herman Josephine , Signal Louise , Areai Danny , Wilson Nick
Published: January 2021

Objective:

To evaluate the impact of changes in import tariffs on sweetened beverages.

Design:

Interrupted time series analysis was used to examine sweetened beverage tariff increases of 40–60 % in 2008 and to 75 % in 2012, and an approximately 11 % decrease in 2014 when an excise tax replaced the tariff. Post-tax trends were compared with a counterfactual modelled on the pre-tax trend for: quarterly price of an indicator beverage, monthly beverage import volumes (both 2001–2017) and quarterly sales volumes (2012–2017). In a controlled analysis, taxed beverage imports were compared with a sugary snacks control.

Setting:

Cook Islands.

Participants:

NA.

Results:

In the first year, after the 2008 tariff increase the price of the selected indicator soft drink increased by 7·3 % (95 % CI 6·3 %, 8·3 %) but after the 2012 tariff increase it decreased by 13·9 % (95 % CI –14·9 %, –12·8 %). At the same time, the import volumes of taxed beverages decreased by 13·2 % (95 % CI –38·1 %, 17·8 %) and 2·9 % (95 % CI –41·6 %, 72·5 %), respectively, and decreased by 24·8 % (95 % CI –36·9, –9·8) and 10·2 % (95 % CI –37·1, 37·5) in the controlled analysis. After the 2014 tax decrease, the price of the indicator soft drink decreased by 23·6 % (95 % CI –26·0 %, –21·1 %), sweetened beverage imports increased by 4·5 % (95 % CI –39·5 %, 156·0 %) and sales of full-sugar soft drinks increased by 31 % (95 % CI –21 %, 243 %).

Conclusions:

The increased import tariffs on sweetened beverages appeared to be effective for reducing import volumes, but this was partly reversed by the reduced tax/tariff in 2014.
Will India's Disengaging Trade Policy Restrict It from Playing a Greater Global Role?
Authors: Palit Amitendu
Published: January 2021

India's ambition of playing a prominent role in regional and global affairs has been particularly visible since the assumption of office by Prime Minister Narendra Modi in May 2014. The ambition has resulted in India's external engagement, abandoning the posturing of non-alignment for a more proactive multi-alignment strategy. Its efforts to engage with major powers such as the US and China, as well as other global middle powers such as Japan, the UK, and Australia, have been positioned on rapid economic progress, enabled by one of the fastest rates of growth among major economies. Attempts to expand global strategic influence, a natural outcome of robust economic expansion, should have seen India pursuing an aggressive outward-oriented external trade policy for increasing its share in global trade. India, though, has shown a marked resistance to open trade, including being reluctant to engage in regional and bilateral trade negotiations. This paper examines the dichotomy between India's desire to play a prominent global role and its aversion to open trade policies. Attributing the inward-looking approach to lack of competitiveness of Indian industry, absence of domestic pro-trade constituencies, and discomfort in negotiating new-generation trade issues, the paper argues India's quest for greater global strategic influence might be adversely affected by its restrictive trade policies.
Inferior vena cava-syndrome
Authors: Klein-Weigel Peter Franz , Elitok Saban , Ruttloff Andreas , Reinhold Sabine , Nielitz Jessica , Steindl Julia , Lutfi Philippe , Rehmenklau-Bremer Lars , Hillner Birgit , Fuchs Heiko , Wrase Christian , Herold Thomas , Beyer Lukas
Published: January 2021

Summary: Inferior vena cava syndrome (IVCS) is caused by agenesis, compression, invasion, or thrombosis of the IVC, or may be associated with Budd-Chiari syndrome. Its incidence and prevalence are unknown. Benign IVCS is separated from malignant IVCS. Both cover a wide clinical spectrum reaching from asymptomatic to highly symptomatic cases correlated to the underlying cause, the acuity, the extent of the venous obstruction, and the recruitment and development of venous collateral circuits. Imaging is necessary to determine the underlying cause of IVCS and to guide clinical decisions. Interventional therapy has changed the therapeutic approach in symptomatic patients. This article provides an overview over IVCS and focuses on interventional therapeutic methods and results.
First Studies of Mesosphere and Lower Thermosphere Dynamics Using a Multistatic Specular Meteor Radar Network Over Southern Patagonia
Authors: Conte J. Federico , Chau Jorge L. , Urco Juan M. , Latteck Ralph , Vierinen Juha , Salvador Jacobo O.
Published: January 2021

This paper presents for the first time results on winds, tides, gradients of horizontal winds, and momentum fluxes at mesosphere and lower thermosphere altitudes over southern Patagonia, one of the most dynamically active regions in the world. For this purpose, measurements provided by SIMONe Argentina are investigated. SIMONe Argentina is a novel multistatic specular meteor radar system that implements a Spread‐spectrum Interferometric Multistatic meteor radar Observing Network (SIMONe) approach, and that has been operating since the end of September 2019. Average counts of more than 30,000 meteor detections per day result in tidal estimates with statistical uncertainties of less than 1 m/s. Thanks to the multistatic configuration, horizontal and vertical gradients of the horizontal winds are obtained, as well as vertical winds free from horizontal divergence contamination. The vertical gradients of both zonal and meridional winds exhibit strong tidal signatures. Mean momentum fluxes are estimated after removing the effects of mean winds using a 4‐h, 8‐km window in time and altitude, respectively. Reasonable statistical uncertainties of the momentum fluxes are obtained after applying a 28‐day averaging. Therefore, the momentum flux estimates presented in this paper represent monthly mean values of waves with periods of 4 h or less, vertical wavelengths shorter than 8 km, and horizontal scales less than 400 km.
Magmatic Processes in the East African Rift System: Insights From a 2015–2020 Sentinel‐1 InSAR Survey
Authors: Albino F. , Biggs J.
Published: January 2021

The East African Rift System (EARS) is composed of around 78 Holocene volcanoes, but relatively little is known about their past and present activity. This lack of information makes it difficult to understand their eruptive cycles, their roles in continental rifting and the threat they pose to the population. Although previous InSAR surveys (1990–2010) showed sign of unrest, the information about the dynamics of the magmatic systems remained limited by low temporal resolution and gaps in the data set. The Sentinel‐1 SAR mission provides open‐access acquisitions every 12 days in Africa and has the potential to produce long‐duration time series for studying volcanic ground deformation at regional scale. Here, we use Sentinel‐1 data to provide InSAR time series along the EARS for the period 2015–2020. We detect 18 ground deformation signals on 14 volcanoes, of which six are located in Afar, six in the Main Ethiopian Rift, and two in the Kenya‐Tanzanian Rift. We detected new episodes of uplift at Tullu Moje (2016) and Suswa (mid‐2018), and enigmatic long‐lived subsidence signals at Gada Ale and Kone. Subsidence signals are related to a variety of mechanisms including the posteruptive evolution of magma reservoirs (e.g., Alu‐Dallafila), the compaction of lava flows (e.g., Nabro), and pore‐pressure changes related to geothermal or hydrothermal activity (e.g., Olkaria). Our results show that ∼20% of the Holocene volcanoes in the EARS deformed during this 5‐years snapshot and demonstrate the diversity of processes occurring.
Saltwater Intrusion in a Mediterranean Delta Under a Changing Climate
Authors: Bellafiore Debora , Ferrarin Christian , Maicu Francesco , Manfè Giorgia , Lorenzetti Giuliano , Umgiesser Georg , Zaggia Luca , Levinson Arnoldo Valle
Published: January 2021

Saltwater intrusion (SWI) in deltas, estuaries, and other coastal areas represents a pressing problem affecting the sustainability of freshwater resources. Observations and numerical experiments are used to investigate SWI in the surface waters of the Italian's largest river delta (the Po Delta) under low discharge conditions. The model successfully reproduced the observed salinity variations along main river branches and in the delta lagoons and investigated fresh and saltwater dynamics during the entire summer 2017. The numerical model is used to explore the hydrological response of the delta system to climate change. The relative effect of controlling factors on saltwater penetration, such as sea‐level rise (SLR), air‐sea fluxes, and reduction of river discharge, was evaluated. Results suggest that changes driven by climate and SLR will exacerbate SWI in the surface waters of the Po Delta system. Extent of SWI in the major river branch is projected to increase up to 80% further into the river. Persistence of SWI at the same site is expected to increase 100% longer. Moreover, additional synthetic simulations were used to investigate the sensitivity of SWI to several river discharges and relative SLR values, highlighting the effects of the two factors in the delta. Such results show different combinations of river discharge and relative SLR values that represent possible scenarios, and are important for managing SWI in river‐sea systems affected by both climatic and anthropogenic factors such as discharge changes from dam construction, land use, and irrigation.
Long‐term Trends in Dissolved Organic Matter Composition and Its Relation to Sea Ice in the Canada Basin, Arctic Ocean (2007–2017)
Authors: DeFrancesco C. , Guéguen C.
Published: January 2021

Absorbance and fluorescence properties of dissolved organic matter (DOM) were measured in the upper and lower polar mixed layer (UPML and LPML, respectively) over an 11‐year period (2007–2017) to assess for yearly changes in the quality and quantity of colored and fluorescent DOM (CDOM and FDOM, respectively) in relation with sea ice concentration in central Canada Basin waters. The LPML waters were enriched in CDOM, total dissolved lignin phenols, terrestrial humic‐like C1, and in microbial humic‐like C2 and C7 relative to the UPML waters (p > 0.05). The low ice years (i.e., 2012, 2016–2017) were characterized by lower humic‐like fluorescence intensity (C4 only) and abundances relative to high ice years (i.e., 2007–2011, 2013–2015), likely the result of the preferential photoalteration of humic material when sea ice concentration was reduced. Significant time increases were found in tryptophan‐like C3 in UPML and terrestrially derived humic‐like C4 in LPML, suggesting an increase in the proteinaceous and terrigenous character of FDOM in UPML and LPML during the 11‐year period, respectively. No interannual variation in dissolved organic carbon concentration was found in LPML and UPML. Weak but positive Spearman correlations were found between the humic‐like intensities and abundances, and sea ice concentration in UPML waters, a consequence of reduced photodegradation in ice covered waters. This 11‐year survey provides the first insight into the influence of summer sea ice concentration and river runoff on the quality and quantity of CDOM and FDOM.
Exploring the Roles of Iron and Irradiance in Dynamics of Diatoms and Phaeocystis in the Amundsen Sea Continental Shelf Water
Authors: Kwon Young Shin , La Hyoung Sul , Jung Jinyoung , Lee Sang Heon , Kim Tae‐Wan , Kang Hyoun‐Woo , Lee SangHoon
Published: January 2021

The Amundsen Sea continental shelf (ACS) water ecosystem is expected to undergo changes since increasing melt rate of glacier and decreasing sea ice extent by global warming would lead to the mitigation of iron and light limitation. We investigated how diatoms and Phaeocystis, two dominant taxa, and primary production in the ACS water would respond to variations in iron and light availabilities by using a 1‐D pelagic ecosystem model. In the model, we added sea ice effects that reduce light penetration and optimized model parameters for diatoms and Phaeocystis. The results from our model showed good agreement with 20‐year observations of Chl‐a as well as the biomass proportion of diatoms and Phaeocystis and nutrient distributions during the growing season. Our model experimental results suggest that the current moderate iron and high light conditions favor the growth of Phaeocystis over diatoms. Moreover, as iron increases, the organic carbon exudation by phytoplankton increases more rapidly than net primary production (NPP), leading to a decline in phytoplankton biomass. On the other hand, irradiance plays a role in controlling NPP in terms of photoinhibition which is reduced by increasing iron. Increases in both iron and irradiance lead to an advance in the timing of the bloom peak (surface Chl‐a maximum) due to increases in phytoplankton carbon loss and photoinhibition. Our results imply that the dominance of Phaeocystis can continue and that the carbon uptake capacity of the ACS in the summer seasons might increase given that iron availability will increase with future climate change.
Using Water Table Depths Inferred From Testate Amoebae to Estimate Holocene Methane Emissions From the Hudson Bay Lowlands, Canada
Authors: Davies M. A. , McLaughlin J. W. , Packalen M. S. , Finkelstein S. A.
Published: January 2021

Wetlands are the largest natural source of methane, yet the roles of source region and paleoclimate in explaining the variability in Holocene atmospheric methane concentrations remain poorly constrained. The Hudson Bay Lowlands (HBL) is one of the world's largest continuous peatland regions and a significant source of methane. We present here, using a novel proxy‐based approach, Holocene methane fluxes for the HBL. Paleo‐methane fluxes were quantified based on water table depth (WTD), inferred from testate amoeba assemblages in nine peat records. WTDs were reconstructed using a North American transfer function and were used to estimate paleo‐methane flux through a linear regression model of contemporary growing season methane fluxes and WTDs from 88 sites across the region. Following HBL peatland initiation in the Middle Holocene, total methane flux is closely related to the increasing area of land emerging from below sea level, controlled by rapid rates of glacial isostatic adjustment. In the Late Holocene, rates of uplift slowed, but methane fluxes remained high due to lower evapotranspiration in a wetter and cooler climate. We estimate that 4.8 ± 1.6 Pg C has been released from HBL peatlands to the atmosphere as CH4 over the last 8,000 years, with an average annual methane emission of 1.1 Tg CH4 yr−1 in the Late Holocene. The values estimated here are broadly consistent with those calculated from other independent methods, on modern and Holocene timescales, demonstrating that testate amoeba records provide an effective approach for scaling local processes to regional paleo‐methane emissions.
New Magnetostratigraphic Insights From Iceberg Alley on the Rhythms of Antarctic Climate During the Plio‐Pleistocene
Authors: Reilly Brendan T. , Tauxe Lisa , Brachfeld Stefanie , Raymo Maureen , Bailey Ian , Hemming Sidney , Weber Michael E. , Williams Trevor , Garcia Marga , Guitard Michelle , Martos Yasmina M. , Pérez Lara F. , Zheng Xufeng , Armbrecht Linda , Cardillo Fabricio G. , Du Zhiheng , Fauth Gerson , Glueder Anna , Gutjahr Marcus , Hernández‐Almeida Iván , Hoem Frida S. , Hwang Ji‐Hwan , Iizuka Mutsumi , Kato Yuji , Kenlee Bridget , O’Connell Suzanne , Peck Victoria , Ronge Thomas A. , Seki Osamu , Tripathi Shubham , Warnock Jonathan
Published: January 2021

International Ocean Discovery Program (IODP) Expedition 382 in the Scotia Sea’s Iceberg Alley recovered among the most continuous and highest resolution stratigraphic records in the Southern Ocean near Antarctica spanning the last 3.3 Myr. Sites drilled in Dove Basin (U1536/U1537) have well‐resolved magnetostratigraphy and a strong imprint of orbital forcing in their lithostratigraphy. All magnetic reversals of the last 3.3 Myr are identified, providing a robust age model independent of orbital tuning. During the Pleistocene, alternation of terrigenous versus diatomaceous facies shows power in the eccentricity and obliquity frequencies comparable to the amplitude modulation of benthic δ18O records. This suggests that variations in Dove Basin lithostratigraphy during the Pleistocene reflect a similar history as globally integrated ice volume at these frequencies. However, power in the precession frequencies over the entire ∼3.3 Myr record does not match the amplitude modulation of benthic δ18O records, suggesting Dove Basin contains a unique record at these frequencies. Comparing the position of magnetic reversals relative to local facies changes in Dove Basin and the same magnetic reversals relative to benthic δ18O at North Atlantic IODP Site U1308, we demonstrate Dove Basin facies change at different times than benthic δ18O during intervals between ∼3 and 1 Ma. These differences are consistent with precession phase shifts and suggest climate signals with a Southern Hemisphere summer insolation phase were recorded around Antarctica. If Dove Basin lithology reflects local Antarctic ice volume changes, these signals could represent ice sheet precession‐paced variations not captured in benthic δ18O during the 41‐kyr world.
Deglacial Ventilation Changes in the Deep Southwest Pacific
Authors: Dai Yuhao , Yu Jimin , A. Rafter Patrick
Published: January 2021

Processes underlying changes in the oceanic carbon storage during the Last Glacial Maximum and the subsequent deglaciation are not fully understood. Here, we present a new high‐resolution radiocarbon reconstruction (expressed as δ14R) at the depth of the modern Lower Circumpolar Deep Water from the Pacific Sector of the Southern Ocean. Our record shows δ14R increases during Heinrich Stadial 1 and the Younger Dryas that agree with the deep‐to‐shallow transfer of old carbon in the Southern Ocean during these two periods. Our record also shows, for the first time, a clear ∼80‰ decline in δ14R during the Antarctic Cold Reversal (ACR), indicating the development of poorly ventilated conditions in the deep Southwest Pacific. These conditions are consistent with the increased Southern Ocean sea‐ice and associated stratification between Upper and Lower Circumpolar Deep Waters. This enhanced stratification in the deep South Pacific possibly facilitated greater carbon storage in the ocean interior during the ACR, effectively limiting oceanic CO2 release and contributing to the atmospheric CO2 plateau as observed in ice cores at that time.
Angular Superresolution Based on A Priori Information
Authors: Lagovsky B. , Samokhin A. , Shestopalov Y.
Published: January 2021

The results of theoretical studies and mathematical modeling indicate the possibility of obtaining the angular superresolution and its limits by using algebraic methods of imaging. The necessary algorithms are created on the basis of solution to inverse problems. The limiting levels of the achieved angular superresolution are found depending on the signal‐to‐noise ratio for objects of various types. A number of specific advantages of the method are shown as applied to the solution of two‐dimensional problems. Capabilities of the method are illustrated by examples. High performance of the proposed approach allows one to use it in real time when scanning and tracking targets.
Zooplankton carcasses stimulate microbial turnover of allochthonous particulate organic matter
Authors: Neubauer Darshan , Kolmakova Olesya , Woodhouse Jason , Taube Robert , Mangelsdorf Kai , Gladyshev Michail , Premke Katrin , Grossart Hans-Peter
Published: January 2021

Carbon turnover in aquatic environments is dependent on biochemical properties of organic matter (OM) and its degradability by the surrounding microbial community. Non-additive interactive effects represent a mechanism where the degradation of biochemically persistent OM is stimulated by the provision of bioavailable OM to the degrading microbial community. Whilst this is well established in terrestrial systems, whether it occurs in aquatic ecosystems remains subject to debate. We hypothesised that OM from zooplankton carcasses can stimulate the degradation of biochemically persistent leaf material, and that this effect is influenced by the daphnia:leaf OM ratio and the complexity of the degrading microbial community. Fresh Daphnia magna carcasses and 13C-labelled maize leaves (Zea mays) were incubated at different ratios (1:1, 1:3 and 1:5) alongside either a complex microbial community (<50 µm) or solely bacteria (<0.8 µm). 13C stable-isotope measurements of CO2 analyses were combined with phospholipid fatty acids (PLFA) analysis and DNA sequencing to link metabolic activities, biomass and taxonomic composition of the microbial community. Our experiments indicated a significantly higher respiration of leaf-derived C when daphnia-derived OM was most abundant (i.e. daphnia:leaf OM ratio of 1:1). This process was stronger in a complex microbial community, including eukaryotic microorganisms, than a solely bacterial community. We concluded that non-additive interactive effects were a function of increased C–N chemodiversity and microbial complexity, with the highest net respiration to be expected when chemodiversity is high and the degrading community complex. This study indicates that identifying the interactions and processes of OM degradation is one important key for a deeper understanding of aquatic and thus global carbon cycle.
Cyrius: accurate CYP2D6 genotyping using whole-genome sequencing data
Authors: Chen Xiao , Shen Fei , Gonzaludo Nina , Malhotra Alka , Rogert Cande , Taft Ryan J. , Bentley David R. , Eberle Michael A.
Published: January 2021

Responsible for the metabolism of ~21% of clinically used drugs, CYP2D6 is a critical component of personalized medicine initiatives. Genotyping CYP2D6 is challenging due to sequence similarity with its pseudogene paralog CYP2D7 and a high number and variety of common structural variants (SVs). Here we describe a novel bioinformatics method, Cyrius, that accurately genotypes CYP2D6 using whole-genome sequencing (WGS) data. We show that Cyrius has superior performance (96.5% concordance with truth genotypes) compared to existing methods (84–86.8%). After implementing the improvements identified from the comparison against the truth data, Cyrius’s accuracy has since been improved to 99.3%. Using Cyrius, we built a haplotype frequency database from 2504 ethnically diverse samples and estimate that SV-containing star alleles are more frequent than previously reported. Cyrius will be an important tool to incorporate pharmacogenomics in WGS-based precision medicine initiatives.
Oxidative stress activates NORAD expression by H3K27ac and promotes oxaliplatin resistance in gastric cancer by enhancing autophagy flux via targeting the miR-433-3p
Authors: Wang Jizhao , Sun Yuchen , Zhang Xing , Cai Hui , Zhang Cheng , Qu Hangying , Liu Lin , Zhang Mingxin , Fu Junke , Zhang Jia , Wang Jiansheng , Zhang Guangjian
Published: January 2021

Oxaliplatin resistance undermines its curative effects on cancer and usually leads to local recurrence. The oxidative stress induced DNA damage repair response is an important mechanism for inducing oxaliplatin resistance by activating autophagy. ELISA is used to detect target genes expression. TMT-based quantitative proteomic analysis was used to investigate the potential mechanisms involved in NORAD interactions based on GO analysis. Transwell assays and apoptosis flow cytometry were used for biological function analysis. CCK-8 was used to calculate IC50 and resistance index (RI) values. Dual-luciferase reporter gene assay, RIP and ChIP assays, and RNA pull-down were used to detect the interaction. Autophagy flux was evaluated using electron microscope and western blotting. Oxidative stress was enhanced by oxaliplatin; and oxaliplatin resistance gastric cancer cell showed lower oxidative stress. TMT labeling showed that NORAD may regulate autophagy flux. NORAD was highly expressed in oxaliplatin-resistant tissues. In vitro experiments indicate that NORAD knockdown decreases the RI (Resistance Index). Oxaliplatin induces oxidative stress and upregulates the expression of NORAD. SGC-7901 shows enhanced oxidative stress than oxaliplatin-resistant cells (SGC-7901-R). NORAD, activated by H3K27ac and CREBBP, enhanced the autophagy flux in SGC-7901-R to suppress the oxidative stress. NORAD binds to miR-433-3p and thereby stabilize the ATG5- ATG12 complex. Our findings illustrate that NORAD, activated by the oxidative stress, can positively regulate ATG5 and ATG12 and enhance the autophagy flux by sponging miR-433-3p. NORAD may be a potential biomarker for predicting oxaliplatin resistance and mediating oxidative stress, and provides therapeutic targets for reversing oxaliplatin resistance.
Single-cell analysis reveals the intra-tumor heterogeneity and identifies MLXIPL as a biomarker in the cellular trajectory of hepatocellular carcinoma
Authors: Dong Xiao , Wang Fan , Liu Chuan , Ling Jing , Jia Xuebing , Shen Feifei , Yang Ning , Zhu Sibo , Zhong Lin , Li Qi
Published: January 2021

Hepatocellular carcinoma (HCC) is a globally prevailing cancer with a low 5-year survival rate. Little is known about its intricate gene expression profile. Single-cell RNA sequencing is an indispensable tool to explore the genetic characteristics of HCC at a more detailed level. In this study, we profiled the gene expression of single cells from human HCC tumor and para-tumor tissues using the Smart-seq 2 sequencing method. Based on differentially expressed genes, we identified heterogeneous subclones in HCC tissues, including five HCC and two hepatocyte subclones. We then carried out hub-gene co-network and functional annotations analysis followed pseudo-time analysis with regulated transcriptional factor co-networks to determine HCC cellular trajectory. We found that MLX interacting protein like (MLXIPL) was commonly upregulated in the single cells and tissues and associated with a poor survival rate in HCC. Mechanistically, MLXIPL activation is crucial for promoting cell proliferation and inhibits cell apoptosis by accelerating cell glycolysis. Taken together, our work identifies the heterogeneity of HCC subclones, and suggests MLXIPL might be a promising therapeutic target for HCC.
Structure of SRSF1 RRM1 bound to RNA reveals an unexpected bimodal mode of interaction and explains its involvement in SMN1 exon7 splicing
Authors: Cléry Antoine , Krepl Miroslav , Nguyen Cristina K. X. , Moursy Ahmed , Jorjani Hadi , Katsantoni Maria , Okoniewski Michal , Mittal Nitish , Zavolan Mihaela , Sponer Jiri , Allain Frédéric H.-T.
Published: January 2021

The human prototypical SR protein SRSF1 is an oncoprotein that contains two RRMs and plays a pivotal role in RNA metabolism. We determined the structure of the RRM1 bound to RNA and found that the domain binds preferentially to a CN motif (N is for any nucleotide). Based on this solution structure, we engineered a protein containing a single glutamate to asparagine mutation (E87N), which gains the ability to bind to uridines and thereby activates SMN exon7 inclusion, a strategy that is used to cure spinal muscular atrophy. Finally, we revealed that the flexible inter-RRM linker of SRSF1 allows RRM1 to bind RNA on both sides of RRM2 binding site. Besides revealing an unexpected bimodal mode of interaction of SRSF1 with RNA, which will be of interest to design new therapeutic strategies, this study brings a new perspective on the mode of action of SRSF1 in cells.
PKA drives an increase in AMPA receptor unitary conductance during LTP in the hippocampus
Authors: Park Pojeong , Georgiou John , Sanderson Thomas M. , Ko Kwang-Hee , Kang Heather , Kim Ji-il , Bradley Clarrisa A. , Bortolotto Zuner A. , Zhuo Min , Kaang Bong-Kiun , Collingridge Graham L.
Published: January 2021

Long-term potentiation (LTP) at hippocampal CA1 synapses can be expressed by an increase either in the number (N) of AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptors or in their single channel conductance (γ). Here, we have established how these distinct synaptic processes contribute to the expression of LTP in hippocampal slices obtained from young adult rodents. LTP induced by compressed theta burst stimulation (TBS), with a 10 s inter-episode interval, involves purely an increase in N (LTPN). In contrast, either a spaced TBS, with a 10 min inter-episode interval, or a single TBS, delivered when PKA is activated, results in LTP that is associated with a transient increase in γ (LTPγ), caused by the insertion of calcium-permeable (CP)-AMPA receptors. Activation of CaMKII is necessary and sufficient for LTPN whilst PKA is additionally required for LTPγ. Thus, two mechanistically distinct forms of LTP co-exist at these synapses.
Male fertility in Arabidopsis requires active DNA demethylation of genes that control pollen tube function
Authors: Khouider Souraya , Borges Filipe , LeBlanc Chantal , Ungru Alexander , Schnittger Arp , Martienssen Robert , Colot Vincent , Bouyer Daniel
Published: January 2021

Active DNA demethylation is required for sexual reproduction in plants but the molecular determinants underlying this epigenetic control are not known. Here, we show in Arabidopsis thaliana that the DNA glycosylases DEMETER (DME) and REPRESSOR OF SILENCING 1 (ROS1) act semi-redundantly in the vegetative cell of pollen to demethylate DNA and ensure proper pollen tube progression. Moreover, we identify six pollen-specific genes with increased DNA methylation as well as reduced expression in dme and dme;ros1. We further show that for four of these genes, reinstalling their expression individually in mutant pollen is sufficient to improve male fertility. Our findings demonstrate an essential role of active DNA demethylation in regulating genes involved in pollen function.
Mathematical model of COVID-19 intervention scenarios for São Paulo—Brazil
Authors: Pinto Neto Osmar , Kennedy Deanna M. , Reis José Clark , Wang Yiyu , Brizzi Ana Carolina Brisola , Zambrano Gustavo José , de Souza Joabe Marcos , Pedroso Wellington , de Mello Pedreiro Rodrigo Cunha , de Matos Brizzi Bruno , Abinader Ellysson Oliveira , Zângaro Renato Amaro
Published: January 2021

With COVID-19 surging across the world, understanding the effectiveness of intervention strategies on transmission dynamics is of primary global health importance. Here, we develop and analyze an epidemiological compartmental model using multi-objective genetic algorithm design optimization to compare scenarios related to strategy type, the extent of social distancing, time window, and personal protection levels on the transmission dynamics of COVID-19 in São Paulo, Brazil. The results indicate that the optimal strategy for São Paulo is to reduce social distancing over time with a stepping-down reduction in the magnitude of social distancing every 80-days. Our results also indicate that the ability to reduce social distancing depends on a 5–10% increase in the current percentage of people strictly following protective guidelines, highlighting the importance of protective behavior in controlling the pandemic. Our framework can be extended to model transmission dynamics for other countries, regions, states, cities, and organizations.
Low-dose decitabine priming endows CAR T cells with enhanced and persistent antitumour potential via epigenetic reprogramming
Authors: Wang Yao , Tong Chuan , Dai Hanren , Wu Zhiqiang , Han Xiao , Guo Yelei , Chen Deyun , Wei Jianshu , Ti Dongdong , Liu Zongzhi , Mei Qian , Li Xiang , Dong Liang , Nie Jing , Zhang Yajing , Han Weidong
Published: January 2021

Insufficient eradication capacity and dysfunction are common occurrences in T cells that characterize cancer immunotherapy failure. De novo DNA methylation promotes T cell exhaustion, whereas methylation inhibition enhances T cell rejuvenation in vivo. Decitabine, a DNA methyltransferase inhibitor approved for clinical use, may provide a means of modifying exhaustion-associated DNA methylation programmes. Herein, anti-tumour activities, cytokine production, and proliferation are enhanced in decitabine-treated chimeric antigen receptor T (dCAR T) cells both in vitro and in vivo. Additionally, dCAR T cells can eradicate bulky tumours at a low-dose and establish effective recall responses upon tumour rechallenge. Antigen-expressing tumour cells trigger higher expression levels of memory-, proliferation- and cytokine production-associated genes in dCAR T cells. Tumour-infiltrating dCAR T cells retain a relatively high expression of memory-related genes and low expression of exhaustion-related genes in vivo. In vitro administration of decitabine may represent an option for the generation of CAR T cells with improved anti-tumour properties.
Role of dams in reducing global flood exposure under climate change
Authors: Boulange Julien , Hanasaki Naota , Yamazaki Dai , Pokhrel Yadu
Published: January 2021

Globally, flood risk is projected to increase in the future due to climate change and population growth. Here, we quantify the role of dams in flood mitigation, previously unaccounted for in global flood studies, by simulating the floodplain dynamics and flow regulation by dams. We show that, ignoring flow regulation by dams, the average number of people exposed to flooding below dams amount to 9.1 and 15.3 million per year, by the end of the 21stcentury (holding population constant), for the representative concentration pathway (RCP) 2.6 and 6.0, respectively. Accounting for dams reduces the number of people exposed to floods by 20.6 and 12.9% (for RCP2.6 and RCP6.0, respectively). While environmental problems caused by dams warrant further investigations, our results indicate that consideration of dams significantly affect the estimation of future population exposure to flood, emphasizing the need to integrate them in model-based impact analysis of climate change.