bluuebunny/crossref_metadata_2025 huggingface dataset:
EXPLORATORY STRUCTURAL EQUATION MODELING IN SECOND LANGUAGE RESEARCH
Authors: Alamer Abdullah , Marsh Herbert
Published: January 2022

This study offers methodological synergy in the examination of factorial structure in second language (L2) research. It illustrates the effectiveness and flexibility of the recently developed exploratory structural equation modeling (ESEM) method, which integrates the advantages of exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) into one complete measurement model. Two sets of data were collected using the L2 Passion Scale, which measures a dualistic model of passion. Study 1 participants were 220 L2 students. A comparison was made between the CFA and the ESEM models. The results demonstrated the superiority of the ESEM method relative to CFA in terms of better goodness-of-fit indices and realistic correlated factors. These results were replicated in another sample of 272 L2 students, providing support for the predictive validity using a structural ESEM model. Guidelines are provided and Mplus syntax files (codes) are included to help analysts apply the methods. We also make the data available publicly. Overall, this research demonstrated the usefulness of ESEM for examining the construct, discriminant, and convergent validity of L2 scales over CFA.
Public health impact of mass sporting and cultural events in a rising COVID-19 prevalence in England
Authors: Smith Jenifer A. E. , Hopkins Susan , Turner Charlie , Dack Kyle , Trelfa Anna , Peh Jerlyn , Monks Paul S.
Published: January 2022

A subset of events within the UK Government Events Research Programme (ERP), developed to examine the risk of transmission of COVID-19 from attendance at events, was examined to explore the public health impact of holding mass sporting events. We used contact tracing data routinely collected through telephone interviews and online questionnaires, to describe the potential public health impact of the large sporting and cultural events on potential transmission and incidence of COVID-19. Data from the EURO 2020 matches hosted at Wembley identified very high numbers of individuals who tested positive for COVID-19 and were traced through NHS Test & Trace. This included both individuals who were potentially infectious (3036) and those who acquired their infection during the time of the Final (6376). This is in contrast with the All England Lawn Tennis Championships at Wimbledon, where there were similar number of spectators and venue capacity but there were lower total numbers of potentially infectious cases (299) and potentially acquired cases (582). While the infections associated with the EURO 2020 event may be attributed to a set of socio-cultural circumstances which are unlikely to be replicated for the forthcoming sporting season, other aspects may be important to consider including mitigations for spectators to consider such as face coverings when travelling to and from events, minimising crowding in poorly ventilated indoor spaces such as bars and pubs where people may congregate to watch events, and reducing the risk of aerosol exposure through requesting that individuals avoid shouting and chanting in large groups in enclosed spaces.
Childhood parenting and adolescent internalizing and externalizing symptoms: Moderation by multilocus hypothalamic–pituitary–adrenal axis-related genetic variation
Authors: Cao Cong , Rijlaarsdam Jolien
Published: January 2022

Genetic variants that regulate hypothalamic–pituitary–adrenal (HPA) axis function have been demonstrated to moderate the association between parenting and mental health. However, extant research has focused primarily on (i) effects of individual genes or (ii) maternal as opposed to paternal parenting. Using a multilocus genetic profile score (MGPS) approach, the current study is the first to examine the moderation effect of multilocus HPA-axis related genetic variants on the association of both maternal and paternal parenting with adolescent internalizing and externalizing symptoms. In a sample of 772 Chinese Han adolescents (Mage = 16.48 ± 1.40 years; 50.1% girls), a theory-driven MGPS was calculated using six polymorphisms within HPA-axis related genes (CRHR1, NR3C1, NR3C2, FKBP5, COMT, and HT1RA). Results showed that the MGPS interacted with both maternal and paternal parenting in the association with adolescent internalizing symptoms, but not externalizing symptoms. Consistent with the differential susceptibility model, adolescents with high versus low MGPS exhibited not only more internalizing symptoms when exposed to low quality of parenting but also less internalizing symptoms when exposed to high quality of parenting. The current findings highlight the potential value of using a multilocus approach to understanding gene-by-environment interaction (G×E) effects underlying mental health. Within such G×E effects, not only maternal but also paternal parenting should be addressed.
Corporatism in Early Twentieth-Century Britain: Three Alternatives for a Post-Liberal Order
Authors: Torreggiani Valerio
Published: January 2022

This article engages with the most recent literature on the global circulation of corporatist projects, discussing three reform schemes elaborated in Britain during the first half of the twentieth century – G.D.H. Cole's guild socialism, Dudley Docker's technocratic business parliament and Harold Macmillan's conservative industrial self-government. Overcoming the often too rigid equivalences between corporatism and fascism, this article seeks to ascertain to what extent and with what nuances corporatist ideas circulated among non-fascist political circles in Britain. It is argued that the schemes analysed shared a similar corporatist matrix, which nonetheless served as the core idea of different political strategies. In the conclusions, it is claimed that these dissimilarities are consequential to the degree of adherence to the principles of capitalism, i.e. the profit-earning motive and the private ownership of the means of production, as well as to the democratic level of the institutions proposed.
The correlation between food insecurity and infant mortality in North Carolina
Authors: Cassidy-Vu Lisa , Way Victoria , Spangler John
Published: January 2022

Objective:

Food insecurity (FI) affects approximately 11·1 % of US households and is related to worsened infant outcomes. Evidence in lower income countries links FI and infant mortality rates (IMR), but there are limited data in the USA. This study examines the relationship between FI and IMR in North Carolina (NC).

Design:

NC county-level health data were used from the 2019 Robert Woods Johnson Foundation County Health Rankings. The dependent variable was county-level IMR. Eighteen county-level independent variables were selected and a multivariable linear regression was performed. The independent variable, FI, was based on the United States Department of Agriculture’s Food Security Supplement to the Current Population Survey.

Setting:

NC counties.

Participants:

Residents of NC, county-level data.

Results:

The mean NC county-level IMR was 7·9 per 1000 live births compared with 5·8 nationally. The average percentage of county population reporting FI was 15·4 % in the state v. 11·8 % nationally. Three variables statistically significantly predicted county IMR: percent of county population reporting FI; county population and percent population with diabetes (P values, respectively, < 0·04; < 0·05; < 0·03). These variables explained 42·4 % of the variance of county-level IMR. With the largest standardised coefficient (0·247), FI was the strongest predictor of IMR.

Conclusions:

FI, low birth weight and diabetes are positively correlated with infant mortality. While correlation is not causation, addressing FI as part of multifaceted social determinants of health might improve county-level IMR in NC.
UV Autofluorescence Microscopy of Oklahoma Permian Synapsid Femur (DimetrodonCope, 1878) Reveals Blood Clots in Vascular Canals
Authors: Armitage Mark H.
Published: January 2022

Dimetrodonsp. femur, jaw, teeth, and rib bones were collected at N.E. Frederick, OK, and sectioned for histological examination. This Oklahoma Museum of Natural History site has yielded well-preserved Paleozoic fossils for decades. All bones were heavily infiltrated with calcite and other minerals, yet a reddish-brown mass obstructed many vascular channels. This reddish-brown mass reacted to 374 nm UV illumination by emitting bright blue autofluorescence. This was true for every specimen and indicates a heavy presence of iron. We conclude that the iron in the canals is the crystallized remains of blood that clotted during an asphyxiation event that killed the animal. Remarkably similar reddish-brown obstructive material has also been observed in other histological studies performed onDimetrodonbones. We conclude that these are also the remains of blood clots and simply await examination under UV fluorescence.
Magma Mixing During Conduit Flow is Reflected in Melt‐Inclusion Data From Persistently Degassing Volcanoes
Authors: Wei Zihan , Qin Zhipeng , Suckale Jenny
Published: January 2022

Persistent volcanic activity is thought to be linked to degassing, but volatile transport at depth cannot be observed directly. Instead, we rely on indirect constraints, such as CO2‐H2O concentrations in melt inclusions trapped at different depth, but this data is rarely straight‐forward to interpret. In this study, we integrate a multiscale conduit‐flow model for non‐eruptive conditions and a volatile‐concentration model to compute synthetic profiles of volatile concentrations for different flow conditions and CO2 fluxing. We find that actively segregating bubbles in the flow enhance the mixing of volatile‐poor and volatile‐rich magma in vertical conduit segments, even if the radius of these bubbles is several orders of magnitude smaller than the width of the conduit. This finding suggests that magma mixing is common in volcanic systems when magma viscosities are low enough to allow for bubble segregation as born out by our comparison with melt‐inclusion data: Our simulations show that even a small degree of mixing leads to volatile concentration profiles that are much more comparable to observations than either open‐ or closed‐system degassing trends for both Stromboli and Mount Erebus. Our results also show that two of the main processes affecting observed volatile concentrations, magma mixing and CO2 fluxing, leave distinct observational signatures, suggesting that tracking them jointly could help better constrain changes in conduit flow. We argue that disaggregating melt‐inclusion data based on the eruptive behavior at the time could advance our understanding of how conduit flow changes with eruptive regimes.
The Response of Northern Hemisphere Polar Lows to Climate Change in a 25 km High‐Resolution Global Climate Model
Authors: Bresson H. , Hodges K. I. , Shaffrey L. C. , Zappa G. , Schiemann R.
Published: January 2022

Polar lows (PLs) are small, intense cyclones that form at high latitudes during the winter. Their high wind speeds and heavy precipitation can have substantial impacts on shipping, coastal communities and infrastructure. However, low‐resolution climate models poorly simulate PLs, which reduces the confidence in their future projections. In this study, Northern Hemisphere (NH) PLs are assessed for the first time in a high‐resolution (25 km) global atmosphere‐only climate model, N512 HadGEM3‐GA3, for both present‐day and future RCP8.5 climate scenarios. The representation of PLs is found to agree reasonably well with the NCEP‐CFS reanalysis. The number of NH PLs are projected to substantially decrease (by over 60%) by the end of the 21st century, which is largely due to an increase in atmospheric static stability. Large decreases in PL activity are found in the Norwegian Sea, north‐east Atlantic and north‐west Pacific Oceans. Smaller changes are found in regions of current PL activity, such as the Barents and Labrador Seas, while new regions of PL activity along the northern Russian coastline are found where the Arctic sea ice is projected to disappear. The spatial differences found in future PL activity could have a substantial impact on human activity in the Arctic region.
Quality of Sediment Organic Matter Determines the Intertidal N2O Response to Global Warming
Authors: Chen Shu , Wang Dongqi , Yu Zhongjie , Nie Jiaqin , Chen Jie , Li Yangjie , Zhang Xiaoli , Chen Zhenlou
Published: January 2022

Estuaries and coasts are areas of intense biogeochemical cycling and are sensitive to global climate change. However, the effect of temperature increase on the emissions of the powerful greenhouse gas nitrous oxide (N2O) in different estuarine and coastal areas is still uncertain. In this study, we used laboratory incubation experiments to investigate increasing temperatures (12, 25, and 35°C) and tidal effects on N2O fluxes in intertidal sediments from the East China coast (ECC). Overall, the ECC acts as a net source of atmospheric N2O and exhibited considerable spatial variability over three orders of magnitude (from −0.17 to 8.4 μmol m−2 h−1). The warming promoted N2O emissions in most intertidal areas, while reducing N2O emissions at some sampling sites. In addition, the overall effect of flooding on N2O emissions changed from a positive to a negative effect with increasing temperature. By combining the sediment properties of all the sampling sites, we found that large differences in N2O emissions at the same amended floodwater nitrogen concentration were due to the quality and quantity of sediment organic matter. Sediment derived mainly from marine sources emitted more N2O than sediment derived from terrestrial sources. This suggests that the mangroves, salt marshes, and intertidal zones of estuaries have a mitigating effect on N2O emissions due to their elevated terrestrial organic matter inputs. This research improves our understanding of the impact of future global climatic changes on intertidal N2O fluxes, which can inform future studies and models and can be used to constrain intertidal N2O emissions.
Inference of Parameters for a Global Hydrological Model: Identifiability and Predictive Uncertainties of Climate‐Based Parameters
Authors: Yoshida T. , Hanasaki N. , Nishina K. , Boulange J. , Okada M. , Troch P. A.
Published: January 2022

Calibration of global hydrological models (GHMs) has been attempted for over two decades; however, an effective and generic calibration method has not been explored. We present a novel framework for calibrating GHMs assuming that parameters can be regionalized by climate similarities. We calibrated four sensitive parameters of the H08 global hydrological model by aggregating the results of 5,000 simulations with randomly generated parameters into 11 Köppen climate classes and using an objective function Nash–Sutcliffe Efficiency (NSE) with random sampling from the proposed parameter distribution. From a 100‐fold split‐sampling test, we found that both the representativeness and robustness of the transferred parameter sets were guaranteed when the upper 5% of the samples were accepted and assign the median of each accepted parameter distribution for the climate class. The simulation with the climate‐based parameters yielded satisfactory (NSE > 0.0) and good (NSE > 0.5) performances at 480 and 234 stations (61.7% and 30.1% of 777 stations), respectively. The storage capacity (SD) and the conductive coefficient (CD) were sensitive to the climate classes and exhibited well‐constrained distributions of the accepted samples, whereas the recession parameters for the subsurface storage (γ and τ) showed little or no explanatory power to climate. The identified parameters for climate classes exhibited consistency with the physical interpretation of soil formation and efficiencies in vapor transfer. The consistency of the identified parameter values with physical underpinnings indicates that the appropriate parameters were determined, which ensured the robustness of parameters, especially when they are transferred to ungauged watersheds.
Polymer interdigitated pillar electrostatic (PIPE) actuators
Authors: Ni Di , Heisser Ronald , Davaji Benyamin , Ivy Landon , Shepherd Robert , Lal Amit
Published: January 2022

This work reports a three-dimensional polymer interdigitated pillar electrostatic actuator that can produce force densities 5–10× higher than those of biological muscles. The theory of operation, scaling, and stability is investigated using analytical and FEM models. The actuator consists of two high-density arrays of interdigitated pillars that work against a restoring force generated by an integrated flexure spring. The actuator architecture enables linear actuation with higher displacements and pull-in free actuation to prevent the in-use stiction associated with other electrostatic actuators. The pillars and springs are 3D printed together in the same structure. The pillars are coated with a gold–palladium alloy layer to form conductive electrodes. The space between the pillars is filled with liquid dielectrics for higher breakdown voltages and larger electrostatic forces due to the increase in the dielectric constant. We demonstrated a prototype actuator that produced a maximum work density of 54.6 µJ/cc and an electrical-to-mechanical energy coupling factor of 32% when actuated at 4000 V. The device was operated for more than 100,000 cycles with no degradation in displacements. The flexible polymer body was robust, allowing the actuator to operate even after high mechanical force impact, which was demonstrated by operation after drop tests. As it is scaled further, the reported actuator will enable soft and flexible muscle-like actuators that can be stacked in series and parallel to scale the resulting forces. This work paves the way for high-energy density actuators for microrobotic applications.
Vaccines elicit highly conserved cellular immunity to SARS-CoV-2 Omicron
Authors: Liu Jinyan , Chandrashekar Abishek , Sellers Daniel , Barrett Julia , Jacob-Dolan Catherine , Lifton Michelle , McMahan Katherine , Sciacca Michaela , VanWyk Haley , Wu Cindy , Yu Jingyou , Collier Ai-ris Y. , Barouch Dan H.
Published: January 2022

The highly mutated SARS-CoV-2 Omicron (B.1.1.529) variant has been shown to evade a substantial fraction of neutralizing antibody responses elicited by current vaccines that encode the WA1/2020 spike protein1. Cellular immune responses, particularly CD8+ T cell responses, probably contribute to protection against severe SARS-CoV-2 infection2–6. Here we show that cellular immunity induced by current vaccines against SARS-CoV-2 is highly conserved to the SARS-CoV-2 Omicron spike protein. Individuals who received the Ad26.COV2.S or BNT162b2 vaccines demonstrated durable spike-specific CD8+ and CD4+ T cell responses, which showed extensive cross-reactivity against both the Delta and the Omicron variants, including in central and effector memory cellular subpopulations. Median Omicron spike-specific CD8+ T cell responses were 82–84% of the WA1/2020 spike-specific CD8+ T cell responses. These data provide immunological context for the observation that current vaccines still show robust protection against severe disease with the SARS-CoV-2 Omicron variant despite the substantially reduced neutralizing antibody responses7,8.
Laser induced breakdown spectroscopy for the rapid detection of SARS-CoV-2 immune response in plasma
Authors: Berlo K. , Xia W. , Zwillich F. , Gibbons E. , Gaudiuso R. , Ewusi-Annan E. , Chiklis G. R. , Melikechi N.
Published: January 2022

As the SARS-CoV-2 pandemic persists, methods that can quickly and reliably confirm infection and immune status is extremely urgently and critically needed. In this contribution we show that combining laser induced breakdown spectroscopy (LIBS) with machine learning can distinguish plasma of donors who previously tested positive for SARS-CoV-2 by RT-PCR from those who did not, with up to 95% accuracy. The samples were also analyzed by LIBS-ICP-MS in tandem mode, implicating a depletion of Zn and Ba in samples of SARS-CoV-2 positive subjects that inversely correlate with CN lines in the LIBS spectra.
Intergenerational effects of preconception opioids on glucose homeostasis and hepatic transcription in adult male rats
Authors: Toorie Anika M. , Vassoler Fair M. , Qu Fangfang , Slonim Donna , Schonhoff Christopher M. , Byrnes Elizabeth M.
Published: January 2022

Adolescence represents a period of significant neurodevelopment during which adverse experiences can lead to prolonged effects on disease vulnerability, including effects that can impact future offspring. Adolescence is a common period for the initiation of drug use, including the use of opioids. Beyond effects on central reward, opioids also impact glucose metabolism, which can impact the risk of diabetes. Moreover, recent animal models suggest that the effects of adolescent opioids can effect glucose metabolism in future offspring. Indeed, we demonstrated that the adult male offspring of females exposed to morphine for 10 days during adolescence (referred to as MORF1 males) are predisposed to the adverse effects of an obesogenic diet. As adults, MORF1 males fed a high fat moderate sucrose diet (FSD) for just 6 weeks had increased fasting glucose and insulin levels when compared to age-matched offspring of females exposed to saline during adolescence (SALF1 males). Clinically, a similar profile of impaired fasting glucose has been associated with hepatic insulin resistance and an increased risk of non-alcoholic fatty liver disease. Thus, in the current study, we used RNA sequencing to determine whether adult MORF1 males demonstrate significant alterations in the hepatic transcriptome suggestive of alterations in metabolism. Age-matched SALF1 and MORF1 males were fed either FSD or control diet (CD) for 8 weeks. Similar to our previous observations, FSD-maintained MORF1 males gained more weight and displayed both fasting hyperglycemia and hyperinsulinemia when compared to FSD-maintained SALF1 males, with no significant effect on glucagon. No differences in bodyweight or fasting-induce glucose were observed in control diet (CD)-maintained F1 males, although there was a trend for CD MORF1 males to display elevated levels of fasting insulin. Unexpectedly, transcriptional analyses revealed profound differences in the hepatic transcriptome of CD-maintained MORF1 and SALF1 (1686 differentially expressed genes) with no significant differences between FSD-maintained MORF1 and SALF1 males. As changes in the hepatic transcriptome were not revealed under 8 weeks FSD conditions, we extended the feeding paradigm and conducted a glucose tolerance test to determine whether impaired fasting glucose observed in FSD MORF1 males was due to peripheral insulin resistance. Impaired glucose tolerance was observed in both CD and FSD MORF1 males, and to a more limited extent in FSD SALF1 males. These findings implicate intergenerational effects of adolescent morphine exposure on the risk of developing insulin resistance and associated comorbidities, even in the absence of an obesogenic diet.
A kabuli chickpea ideotype
Authors: Eker Tuba , Sari Duygu , Sari Hatice , Tosun Hilal Sule , Toker Cengiz
Published: January 2022

The concept of ‘crop ideotype’ is coined as a desirable plant model expected to better perform for seed yield, oils and other useful characteristics when developed as a cultivar, and it consists of two major approaches, namely, (i) ‘defect elimination’, that is, integration of disease resistance to a susceptible genotype from a resistant genotype and (ii) ‘selection for yield’ by improving yield after crosses between desirable parents. For consideration of these approaches, here we introduced an ideotype in kabuli chickpea (Cicer arietinum L.) which is high-yielding, extra-large-seeded, and double- or multi-podded, has high plant height and imparipinnate-leafed traits, and is heat tolerant and resistant to ascochyta blight [Ascochyta rabiei (Pass.) Labr.], which causes considerable yield losses, via marker-assisted selection. F3 and F4 lines were evaluated for agro-morphological traits divided into six classes, namely, (i) imparipinnate-leafed and single-podded progeny, (ii) imparipinnate-leafed and double-podded progeny, (iii) imparipinnate-leafed and multi-podded progeny, (iv) unifoliolate-leafed and single-podded progeny, (v) unifoliolate-leafed and double-podded progeny, (vi) unifoliolate-leafed and multi-podded progeny. F3:4 lines having 100-seed weight ≥ 45 g and double- or multi-podded traits were additionally assessed for resistance to ascochyta blight using molecular markers including SCY17590 and CaETR-1. Superior lines having higher values than their best parents were determined for all studied traits indicating that economic and important traits including yield and seed size in chickpea could be improved by crossing suitable parents. Imparipinnate-leafed and multi-podded plants had not only the highest number of pods and seeds per plant but also the highest yield. On the other hand, imparipinnate-leafed and single podded progeny had the largest seed size, followed by imparipinnate-leafed and double-podded progeny. Multi-podded plants produced 23% more seed yield than that of single-podded plants, while multi-podded plants attained 7.6% more seed yield than that of double-podded plants. SCY17590 and CaETR-1 markers located on LG4 related to QTLAR2 and QTLAR1 were found in 14 lines among 152 F3:4 lines. Six superior lines were selected for being double- or multi-podded, imparipinnate-leafed, suitable for combine harvest, heat-tolerant, and resistant to ascochyta blight, and having both of two resistance markers and extra-large seeds as high as 50–60 g per 100-seed weight. Resistance alleles from two different backgrounds for resistance to ascochyta blight were integrated with double- or multi-podded kabuli chickpea lines having high yield, extra-large seeds, high plant height, imparipinnate-leaves and high heat tolerance, playing a crucial role for future demands of population and food security. These approaches seem to be applicable in ideotype breeding for other important crop plants.
Bio-tolerance potential and environmental risks assessment of Oreochromis niloticus and Ipomoea aquatica in Agodi Reservoir, Nigeria
Authors: Ogungbile P. O. , Ajibare A. O. , Ayeku P. O. , Akinola J. O.
Published: January 2022

The concentration of nine heavy metals in Oreochromis niloticus and Ipomoea aquatica inhabiting Agodi reservoir, Oyo State, Nigeria were investigated for twelve months. The concentrations of the metals were carried out using PG990 Atomic Absorption Spectrophotometer. The Ecological Risk Quotient (ERQ) was calculated using standard methods while the tolerability was determined with Box Plot analysis. The metal bioaccumulation in O. niloticus and I. aquatica followed the order Mn > Fe > Zn > Cu > Co > Pb > Cd > Cr > Ni and Fe > Zn > Mn > Cu > Pb > Cd > Co > Cr > Ni respectively. The results revealed O. niloticus to bioaccumulate the metals more than I. aquatica. Most of the examined metals were higher than the safety limit for the metals concentration in O. niloticus and I. aquatica. Also, I. aquatica had higher tolerability for heavy metals than O. niloticus. In O. niloticus, metal concentration, as well as ERQ, was higher in the wet season while no particular order was observed for I. aquatica. The ERQ result revealed that Cd, Fe, Mn, Zn, Cu and Pb exhibited a high level of ecological risk to both the aquatic flora and fauna as the ERQ values were above the risk limit of one (1). Thus, there is a significant environmental risk associated with heavy metals in the water body.
The effectiveness of desogestrel for endometrial protection in women with abnormal uterine bleeding-ovulatory dysfunction: a non-inferiority randomized controlled trial
Authors: Soontrapa Nisarath , Rattanachaiyanont Manee , Warnnissorn Malee , Wongwananuruk Thanyarat , Indhavivadhana Suchada , Tanmahasamut Prasong , Techatraisak Kitirat , Angsuwathana Surasak
Published: January 2022

Women with chronic abnormal uterine bleeding-ovulatory dysfunction (AUB-O) are at increased risk of endometrial neoplasia. We conducted a non-inferiority randomized controlled trial to determine the effectiveness of two cyclic-progestin regimens orally administered 10 d/month for 6 months on endometrial protection and menstruation normalization in women with AUB-O. There were 104 premenopausal women with AUB-O randomized to desogestrel (DSG 150 µg/d, n = 50) or medroxyprogesterone acetate (MPA 10 mg/d, n = 54) group. Both groups were comparable in age (44.8 ± 5.7 vs. 42.5 ± 7.1 years), body mass index (24.8 ± 4.7 vs. 24.9 ± 4.7 kg/m2), and AUB characteristics (100% irregular periods). The primary outcome was endometrial response rate (the proportion of patients having complete pseudodecidualization in endometrial biopsies during treatment cycle-1). The secondary outcome was clinical response rate (the proportion of progestin withdrawal bleeding episodes with acceptable bleeding characteristics during treatment cycle-2 to cycle-6). DSG was not inferior to MPA regarding the endometrial protection (endometrial response rate of 78.0% vs. 70.4%, 95% CI of difference − 9.1–24.4%, non-inferiority limit of − 10%), but it was less effective regarding the menstruation normalization (acceptable bleeding rate of 90.0% vs 96.6%, P = 0.016).

Clinical trial registration: ClinicalTrials.gov (NCT02103764, date of approval 18 Feb 2014).
Age related non-type 2 inflammation and its association with treatment outcome in patients with chronic rhinosinusitis with nasal polyp in Korea
Authors: Kim Jeong-Whun , Won Tae-Bin , Woo Hyunjun , Yang Seung Koo , Phannikul Chayakoen , Ko Seung Ah , Kim Hyojin , Rhee Chae-Seo , Cho Sung-Woo
Published: January 2022

This study aimed to investigate the effect of age in patients with chronic rhinosinusitis with nasal polyp (CRSwNP). 269 patients were divided into eosinophilic and non-eosinophilic groups based on tissue eosinophilia, defined by eosinophils accounting for more than 20% of the total inflammatory cells. Patients were then further divided into younger and older groups based on the age of 35 years. Clinical characteristics including blood eosinophil, Lund Mackay score, and modified Lund-Kennedy (mLK) scores were compared. Levels of 14 cytokines from nasal tissues of an additional 78 patients were analyzed. Tissue eosinophilia was significantly associated with age and the proportion of non-eosinophilic CRSwNP was significantly higher in younger patients as compared to older patients (79.2% vs 56.6%). There was no difference in clinical characteristics and cytokine levels between the younger and older patients with eosinophilic CRSwNP. In contrast, in patients with non-eosinophilic CRSwNP, younger patients had significantly lower preoperative blood eosinophils and higher mLK scores at three and six months, postoperatively, compared to older patients. Alpha-1 antitrypsin and IL-5 levels were significantly lower in younger patients than in older patients in non-eosinophilic CRSwNP. This study suggests a potential association between age, non-type 2 inflammation and treatment outcome in CRSwNP.
Feasibility of training the dorsolateral prefrontal-striatal network by real-time fMRI neurofeedback
Authors: Weiss Franziska , Zhang Jingying , Aslan Acelya , Kirsch Peter , Gerchen Martin Fungisai
Published: January 2022

Real-time fMRI neurofeedback (rt-fMRI NF) is a promising non-invasive technique that enables volitional control of usually covert brain processes. While most rt-fMRI NF studies so far have demonstrated the ability of the method to evoke changes in brain activity and improve symptoms of mental disorders, a recently evolving field is network-based functional connectivity (FC) rt-fMRI NF. However, FC rt-fMRI NF has methodological challenges such as respirational artefacts that could potentially bias the training if not controlled. In this randomized, double-blind, yoke-controlled, pre-registered FC rt-fMRI NF study with healthy participants (N = 40) studied over three training days, we tested the feasibility of an FC rt-fMRI NF approach with online global signal regression (GSR) to control for physiological artefacts for up-regulation of connectivity in the dorsolateral prefrontal-striatal network. While our pre-registered null hypothesis significance tests failed to reach criterion, we estimated the FC training effect at a medium effect size at the end of the third training day after rigorous control of physiological artefacts in the offline data. This hints at the potential of FC rt-fMRI NF for the development of innovative transdiagnostic circuit-specific interventional approaches for mental disorders and the effect should now be confirmed in a well-powered study.
Fungal fruit body assemblages are tougher in harsh microclimates
Authors: Krah Franz-Sebastian , Hagge Jonas , Schreiber Jasper , Brandl Roland , Müller Jörg , Bässler Claus
Published: January 2022

Forest species are affected by macroclimate, however, the microclimatic variability can be more extreme and change through climate change. Fungal fruiting community composition was affected by microclimatic differences. Here we ask whether differences in the fruiting community can be explained by morphological traits of the fruit body, which may help endure harsh conditions. We used a dead wood experiment and macrofungal fruit body size, color, and toughness. We exposed logs of two host tree species under closed and experimentally opened forest canopies in a random-block design for four years and identified all visible fruit bodies of two fungal lineages (Basidio- and Ascomycota). We found a consistently higher proportion of tough-fleshed species in harsher microclimates under open canopies. Although significant, responses of community fruit body size and color lightness were inconsistent across lineages. We suggest the toughness-protection hypothesis, stating that tough-fleshed fruit bodies protect from microclimatic extremes by reducing dehydration. Our study suggests that the predicted increase of microclimatic harshness with climate change will likely decrease the presence of soft-fleshed fruit bodies. Whether harsh microclimates also affect the mycelium of macrofungi with different fruit body morphology would complement our findings and increase predictability under climate change.
Evaluation of epigenetic age calculators between preeclampsia and normotensive pregnancies in an Australian cohort
Authors: Pruszkowska-Przybylska Paulina , Brennecke Shaun , Moses Eric K. , Melton Phillip E.
Published: January 2022

Advanced biological aging, as assessed through DNA methylation markers, is associated with several complex diseases. The associations between maternal DNA methylation age and preeclampsia (PE) have not been fully assessed. The aim of this study was to examine if increased maternal DNA methylation age (DNAmAge) was shown to be accelerated in women with PE when compared to women who had normotensive pregnancies. The case/control cohort available for study consisted of 166 women (89 with normotensive pregnancy, 77 with PE) recruited previously at the Royal Women’s Hospital in Melbourne, Australia. DNA methylation profiles were obtained using the Illumina EPIC Infinium array for analysis of genomic DNA isolated from whole blood. These profiles were used to calculate seven estimates of DNAmAge and included (1) Horvath, (2) Hannum, (3) Horvath Skin and Blood, (4) Wu, (5) PhenoAge, (6) telomere length and (7) GrimAge and its surrogate measures. Three measures of DNA methylation age acceleration were calculated for all seven measures using linear regression. Pearson's correlation was performed to investigate associations between chronological age and DNAmAge. Differences between chronological age and DNAmAge and epigenetic age acceleration were investigated using t-tests. No significant difference was observed for chronological age between women with PE (age = 30.53 ± 5.68) and women who had normotensive pregnancies (age = 31.76 ± 4.76). All seven DNAmAge measures were significantly correlated (p < 0.001) with chronological age. After accounting for multiple testing and investigating differences in DNAmAge between normotensive women and women with PE, only Wu DNAmAge was significant (p = 0.001). When examining differences for epigenetic age acceleration between PE and normotensive women Hannum, Wu, and PhenoAge DNAmAge estimates (p < 0.001) were significant for both epigenetic age acceleration and intrinsic acceleration models. We found that accelerated maternal DNAmAge is increased in women with PE in some models of epigenetic aging. This research underlines the importance for further investigation into the potential changes of differential DNA methylation in PE.
The formation of tonalitic and granodioritic melt from Venusian basalt
Authors: Wang Yao Jui , Shellnutt J. Gregory , Kung Jennifer , Iizuka Yoshiyuki , Lai Yu-Ming
Published: January 2022

The crust of Venus is composed of the low lying volcanic planitiae and the elevated, deformed tesserae. It is thought that the tesserae may be composed of silicic igneous rocks and that it may resemble proto-continental crust. The initial development of terrestrial continental crust is likely due to melting and deformation of primitive mafic crust via mantle-plume upwelling and collisional plate processes. Unlike Earth, the lithosphere of Venus is not divided into plates and therefore evolved continental crust, if present, developed primarily by melting of pre-existing mafic crust. Here, we report the results of high pressure equilibrium partial melting experiments using a parental composition similar to the basalt measured at the Venera 14 landing site in order to determine if silicic melts can be generated. It was found that at pressures of 1.5 GPa and 2.0 GPa and temperatures of 1080 °C, 1090 °C, and 1285 °C that tonalitic and granodioritic melts can be generated. The experimental results indicate that silicic rocks may be able to form in the crust of Venus providing the thermal regime is suitable and that the lower crust is basaltic. The implication is that the older, thicker regions of Venusian crust may be partially composed of silicic igneous rocks.
Higher hemoglobin levels are an independent risk factor for gestational diabetes
Authors: Sissala Niina , Mustaniemi Sanna , Kajantie Eero , Vääräsmäki Marja , Koivunen Peppi
Published: January 2022

Incidence of gestational diabetes (GDM) has increased rapidly. It poses significant risks for both mother and fetus affecting also negatively their longer-term metabolic heath. We asked whether early pregnancy maternal hemoglobin (Hb) levels, indicative for tissue oxygenation, would affect mother’s metabolic health and fetal outcome. We assessed in FinnGeDi, a Finnish multicenter case–control study for GDM (n = 1828), association of maternal 1st trimester Hb levels with metabolic parameters and perinatal outcome. Our data show that mothers with GDM had higher Hb levels compared to controls (mean difference 1.746 g/L). Hb levels associated positively with pre-pregnancy body mass index (BMI), fasting glucose levels and glucose levels in a glucose tolerance test and systolic and diastolic blood pressure (bp) levels. When assessed in quartiles the highest Hb quartile had more chronic and gestational hypertension and the most adverse outcome of the metabolic parameters, dose-dependency seen in bp, BMI and glucose levels. In a multivariable regression analysis Hb levels remained an independently associated parameter for GDM after adjusting for key covariates (OR 1.019, 95% CI [1.007; 1.031]). In conclusion, higher maternal Hb levels within the normal variation are an independent risk factor for GDM in this population but have little effect on perinatal outcome.
Higher order interactions destroy phase transitions in Deffuant opinion dynamics model
Authors: Schawe Hendrik , Hernández Laura
Published: January 2022

Most opinion dynamics models are based on pairwise interactions. However in many real situations, discussions take place within groups of people. Here, we define a higher order Deffuant model by generalizing the original pairwise interaction model for bounded-confidence opinion-dynamics to interactions involving a group of agents of size k. The generalized model is naturally encoded in a hypergraph. We study this dynamics in different hypergraph topologies, from random hypergraph ensembles, to spatially embedded hyper-lattices. We show that including higher order interactions induces a drastic change in the onset of consensus for random hypergraphs; instead of the sharp phase transition, characteristic of the dyadic Deffuant model, the system undergoes a smooth size independent crossover to consensus, as the confidence value increases. This phenomenon is absent from regular hypergraphs, which conserve a phase transition.
Role of Academia: Drug Repurposing to Induce Autophagy for Treatment of Neurodegenerative Diseases
Authors: Fernandez-Estevez M. , Wrobel L. , Rubinsztein D. C.
Published: January 2022

The prevalence of neurodegenerative diseases is increasing as the global population ages, and currently none of these late-onset conditions are curable. Therefore, there is an urgent need to understand the mechanisms of disease progression and to find new therapies. Most late-onset neurodegenerative disorders manifest with toxic, aggregate-prone proteins in neurons. Many of these harmful proteins have been shown to be autophagic substrates, and the induction of autophagy reduces their levels and attenuates disease phenotypes in neurodegenerative disease animal models. We and others have examined if existing drugs can be repurposed as new therapeutic agents that induce autophagy to reduce the levels of such toxic proteins. We highlight that a key component of a repurposing project is to test if the drug exposures at conventional doses in humans enable induction of the novel potentially therapeutic repurposing pathway.
Role of Industry
Authors: Hayes D. J. , Escott K. J.
Published: January 2022

Innovative, collaborative partnerships between the pharmaceutical industry, academic groups and funders have provided new opportunities to repurpose compounds forinto new diseases. The ultimate goal of these public–private partnerships is to develop new medicines faster in diseases which have limited or no treatment options and to share optimised compounds to build disease understanding with external scientific experts. This chapter provides examples of how unique collaborations have developed between industry and external researchers over the past 10 years and have enabled novel repositioning research and development with industry assets.
Collaboration Models for Repurposing
Authors: Bloom Bruce
Published: January 2022

Drug repurposing has the promise to quickly deliver safe, efficacious and cost-effective therapies to patients, but is challenging scientifically and commercially. To overcome the challenges, drug repurposing depends on collaboration, from simple physician–patient informed consent to use a drug off label, to complex multiple-party for-profit and not-for-profit partnerships to secure regulatory approval for a new disease indication for an approved drug. These collaborations can range from the serendipitous to the well-planned. This chapter provides examples for different collaborations that have or are pushing drug repurposing forward and highlights opportunities for many types of collaborations that might be employed to drive more drug repurposing to patients.
Screening Technologies
Authors: Sheinerman F.
Published: January 2022

Screening advanced compounds enables discovery of direct repurposing candidates, novel drug-like leads for optimization, and informative pharmacological probes. In this chapter, we describe different types of screening collections used in drug repurposing, discuss issues and considerations in preparing and executing a repurposing screen, and present examples of in vitro and in vivo repurposing assays. We further describe various data sources reporting information on de-risked compounds of different types and illustrate how data mining and chemoinformatic and chemogenomic searches can be used to access large numbers of advanced compounds and assemble collections most suitable for screening in a given disease model. We argue that a view of repurposing screening as a large-scale bet on finding candidates for clinical testing is narrow and incomplete. Rather, when thoughtfully executed, screening of re-risked compounds is informed by target pathobiology and offers a means to efficiently convert advances in the development of sophisticated non-clinical models and new insights in disease mechanisms into novel drug-like leads and candidates for development.
Adapting Payers’ and Producers’ Incentives to Drug Repurposing
Authors: Cole A. , Handelin B. , Cavalla D.
Published: January 2022

As healthcare costs increase, new and sustainable solutions to develop and fund treatment options for patients are paramount. Drug repurposing could offer one such solution, but requires a re-think and adaptation of payers’ and producers’ incentives. In this chapter we describe the considerations of payers, and how these translate to signals for research and development by producers. Payers can send the right signals to incentivise drug repurposing through value-based models of payment, but health systems differ in their willingness and ability to support indication-based pricing. For off-patent/generic drugs, alternative models of funding may be needed. We also elaborate a business model that exchanges some of the profit motives with the prioritisation of medical value. The two approaches described in this chapter are drawn on ways to influence the price for repurposed drugs (a ‘pull’ mechanism) and ways to disincentivise the existing model, which is increasingly recognised as too expensive and inefficient (a ‘push’ mechanism).
Optimization of measurement mode and sample processing for FTIR microspectroscopy in skin cancer research
Authors: Shakya Bijay Ratna , Teppo Hanna-Riikka , Rieppo Lassi
Published: January 2022

The spectra of identical samples measured in two different modes and with or without paraffin show a significant difference. The paraffinized samples measured in transflection mode showed the best accuracy in discriminating two melanoma cell lines.
N-Oxides amplify catalyst reactivity and isoselectivity in the ring-opening polymerization of rac-β-butyrolactone
Authors: Dong Xiang , Brown Alexander M. , Woodside Audra J. , Robinson Jerome R.
Published: January 2022

Experiments and computations establish that donor electronics control activity, while donor sterics control catalyst deactivation.
Coacervate microdroplets incorporating J-aggregates toward photoactive membraneless protocells
Authors: Liu Ziteng , Ji Yanglimin , Mu Wenjing , Liu Xiaodan , Huang Li Yan , Ding Tao , Qiao Yan
Published: January 2022

A photoactive membraneless protocell from cooperative coacervation of J-aggregates and polyelectrolytes via liquid–liquid phase separation offers an efficient energy transduction pathway to confine photocatalytic reactions within compartments.
A specific esterase and pH logically regulate ESIPT: different kinds of granulocyte sorting
Authors: Wang Kui , Feng Beidou , Wang Ge , Cui Jingqiang , Yang Lin , Jiang Kai , Zhang Hua
Published: January 2022

The ESIPT process of HBT-ASDs was synergistically activated by dual-factors, NAS-DCE and pH. They emit logical and differential fluorescence response signals to sort the acid, neutrophil and alkaline granulocytes.
Lack of the ESIPT band of aromatic ortho-aminoaldehyde derivatives triggered by N–H vibration
Authors: Zhou Zhongjun , Zhang Jilong , Qu Zexing
Published: January 2022

The vibronic effect plays an important role in controlling fluorescence emissions of ESIPT reactions for o-aminoaldehyde and ketone derivatives.
Structural adaptations in the bovine serum albumin protein in archetypal deep eutectic solvent reline and its aqueous mixtures
Authors: Kumari Monika , Kumari Pratibha , Kashyap Hemant K.
Published: January 2022

The partial regaining of the BSA protein structure in aqueous medium from a denatured structure adapted in the presence of reline DES.