bluuebunny/crossref_metadata_2025 huggingface dataset:
The potential action of SSRIs in the treatment of skin diseases including atopic dermatitis and slow-healing wounds
Authors: Kiecka Aneta , Szczepanik Marian
Published: October 2022

Selective serotonin reuptake inhibitors (SSRIs) are used to treat affective and anxiety disorders. Antidepressants have also been shown to have antimicrobial and immunomodulatory effects, which may affect the microbiota-intestinal-brain axis. Studies show that SSRIs have antimicrobial activity both in vivo and in vitro and influence bacteria by inhibiting biofilm, affecting efflux pumps, among others. A huge challenge today is the prevention and treatment of skin diseases, including atopic dermatitis (AD) and slow-healing wounds. Skin diseases including AD and non-healing wounds are serious medical problem. People suffering from these conditions feel constant discomfort, which also affects their psychological state. Research on new treatments for AD and slow-healing wounds is essential because current medications are not fully effective and have many side effects. Exploring new drug groups for AD and slow-healing wounds will allow for the creation of an alternative treatment for these diseases. SSRIs represent a hope for the treatment of skin diseases due to their immunomodulatory and antimicrobial properties.
Can we trust measures of trust? Measurement invariance in trust in EU news media
Authors: Sapir Eliyahu V.
Published: October 2022

Trust in the news media received wide scholarly attention for almost a century, which was further boosted as a result of recent developments in the media landscape and changes in how news is made and consumed. Despite that, the conceptualization of trust in the news media is still debated, and its measurement comparability has not yet been established. In this paper, I build up on earlier conceptualizations of trust in the news media, and test three theoretically derived measurement models to determine their cross-cultural equivalence in 28 EU countries. Using Eurobarometer data, I test the validity and comparability of these measurements employing multi-group confirmatory factor analysis. The findings indicate that trust is a unidimensional latent construct, equally interpreted across contexts. People's level of trust in the news media reflects their general attitude to the news stories and reporters in all sources of media they are exposed to. While bifactorial measurements of news media trust, differentiating between legacy and online sources, have some merit in single case-studies, they are non-invariant and therefore non comparable. This means that any cross-population differences found employing them are likely a function of measurement idiosyncrasies or other unknown factors.
An integrated cognitive framework for understanding modern cities
Authors: Guo Renzhong , Hong Wuyang , He Biao , Wang Weixi , Li Xiaoming , Li Minmin , Jiang Lin
Published: October 2022

Modern urban development urgently requires a new management concept and operational mechanism to encourage the exploration of frameworks for cognizing and studying urban characteristics. In the present study, modern cities are first understood from the perspective of their basic theoretical evolution. Each modern city is seen as a complex system of organic life forms. Urban information science propels modern urban research in the direction of rationality. This paper also presents the new characteristics of modern cities (and how they have changed) in relation to external structure and internal functions. It examines the generation of urban problems and governance adaptability. On this basis, this paper proposes a cognitive model for studying modern cities, integrating basic theoretical, methodological support, and governance systems. It discusses the basic rationale and core idea for constructing each of these three systems. The research aims to guide and implement modern urban construction and sustainable development in a more effective way.
Lichtenberg Figures: How a Cutaneous Sign Can Solve Suspicious Death Cases
Authors: Manoubi Syrine Azza , Shimi Maha , Gharbaoui Meriem , Allouche Mohamed
Published: October 2022

Lightning is a natural weather phenomenon that occurs most commonly during the summer months in the afternoon or early evening. Lightning strikes can cause accidental deaths. In developed countries, lightning fatalities occur almost exclusively outdoors. Deaths from lightning may be in remote places with no witnesses. Forensic pathologists may not be able to reach the scene of death because it is too hazardous or inaccessible. Bodies may have neither evidence of skin burns nor torn areas on their clothes. The presumption of accidental death may be difficult to prove. We present 3 cases in which neither the examination of the death scene nor the examination of the bodies by those who attested to the death were performed. The bodies were transported to the morgue for a forensic autopsy because the deaths were considered suspicious. Physicians who attest to death in open spaces during weather that could produce lightning should actively search for Lichtenberg figures, which are considered irrefutable proof of fatal lightning in such settings. They should also photograph them and submit them as evidence. Nevertheless, physicians should keep in mind that Lichtenberg figures are not considered pathognomonic of lightning because some skin manifestations may mimic them.
The Fundamentals of Social Research
Authors: Kellstedt Paul M. , Whitten Guy D. , Tuch Steven A.
Published: October 2022

This textbook provides an introduction to the scientific study of sociology and other social sciences. It offers the basic tools necessary for readers to become both critical consumers and beginning producers of scientific research on society. The authors present an integrated approach to research design and empirical analyses in which researchers can develop and test causal theories. They use examples from social science research that students will find engaging and inspiring and that will help them to understand key concepts. The book makes technical materials accessible to students who might otherwise be intimidated by mathematical examples. This new text, with the addition of sociologist Steven A. Tuch to the author team, follows the successful format, approach, and pedagogical features in Paul M. Kellstedt and Guy D. Whitten's bestselling text, The Fundamentals of Political Science Research, now in its third edition. Workbooks in Stata, SPSS, and R, three of the most popular statistical analysis programs, are available as separate purchases to accompany this textbook, enabling students to connect the lessons of this book to hands-on applications of the software.
John Gunn
Authors: Kennaway George
Published: October 2022

Examines the life and work of Scottish cellist and antiquarian John Gunn (1766-1824) through newly discovered sources.
Cottage Gardens and Gardeners in the East of Scotland, 1750-1914
Authors: Rice Catherine
Published: October 2022

This pioneering study tells the story of the emergence of rural workers' gardens during a period of unprecedented economic and social change in the most dynamic and prosperous region of Scotland.
West African Soldiers in Britain's Colonial Army, 1860-1960
Authors: Stapleton Timothy
Published: October 2022

Explores the history of Britain's colonial army in West Africa, especially the experiences of ordinary soldiers recruited in the region.
Fu Poetry along the Silk Roads
Authors: Kong Xurong
Published: October 2022

This book explores
the dissemination of ideas and information on the early silk
roads between Europe and China, through the first detailed study
of the Sinicization of foreign objects in Chinese poetic writing
of the third century CE.
Maritime Musicians and Performers on Early Modern English Voyages
Authors: Seth James
Published: October 2022

Maritime Musicians and Performers on Early Modern English Voyages aims to tell the full story of early English shipboard performers, who have been historically absent from conversations about English navigation, maritime culture, and economic expansion. Often described reductively in voyaging accounts as having one function, in fact maritime performers served many communicative tasks. Their lives were not only complex, but often contradictory. Though not high-ranking officers, neither were they lower-ranking mariners or sailors. They were influenced by a range of competing cultural practices, having spent time playing on both land and sea, and their roles required them to mediate parties using music, dance, and theatre as powerful forms of nonverbal communication. Their performances transcended and breached boundaries of language, rank, race, religion, and nationality, thereby upsetting conventional practices, improving shipboard and international relations, and ensuring the success of their voyages.
Conquer primal fear: Phonological features are innate and substance-free
Authors: Reiss Charles , Volenec Veno
Published: October 2022

We argue that the representational primes of the human phonological faculty, the so-called distinctive features, are innate and substance-free. Our arguments for the innateness of features are built on traditional and novel logical arguments, experimental evidence accumulating over recent decades, and somewhat detailed proposals about their neurobiological reality. As symbols in the brain, features are substance-free, that is, they are devoid of articulatory and acoustic content, or even any direct reference to such phenomena. This is consistent with our substance-free conception of phonological computation, an approach that eschews functionalist notions like markedness, ease of articulation, and so on. We also outline a neural model of the phonetics-phonology interface called Cognitive Phonetics, which transduces innate features to speech articulation and from speech acoustics. These extra-grammatical transduction procedures are also part of the human biological endowment, which leaves no room for language-specific phonetics in our theory of the externalization of language. We show how Cognitive Phonetics can account for traditionally recognized intersegmental coarticulation, as well as the previously unexplored intrasegmental coarticulation, strongly suggesting that the basic units of speech production are transduced features.
A systemwide approach to validation of electronic device denominator data
Authors: Metzger Kristen E. , Salim Asra A. , Mikolajczak Anessa R. , Dolgin Gina , Barajas Grace M. , Jenkins Charles R. , Silkaitis Christina M.
Published: October 2022

A multidisciplinary team collaborated to develop and validate a process to electronically capture patient and device denominator data at 6 hospitals in the same healthcare system. Validation was completed within 4–16 months. Manual count errors were identified as the main driver of electronic versus manual discrepancies.
A Hamiltonian Dysthe equation for deep-water gravity waves with constant vorticity
Authors: Guyenne Philippe , Kairzhan Adilbek , Sulem Catherine
Published: October 2022

This paper is a study of the water wave problem in a two-dimensional domain of infinite depth in the presence of non-zero constant vorticity. A goal is to describe the effects of uniform shear flow on the modulation of weakly nonlinear quasi-monochromatic surface gravity waves. Starting from the Hamiltonian formulation of this problem and using techniques from Hamiltonian transformation theory, we derive a Hamiltonian Dysthe equation for the time evolution of the wave envelope. Consistent with previous studies, we observe that the uniform shear flow tends to enhance or weaken the modulational instability of Stokes waves depending on its direction and strength. Our method also provides a non-perturbative procedure to reconstruct the surface elevation from the wave envelope, based on the Birkhoff normal form transformation to eliminate all non-resonant triads. This model is tested against direct numerical simulations of the full Euler equations and against a related Dysthe equation derived recently by Curtis, Carter & Kalisch (J. Fluid Mech., vol. 855, 2018, pp. 322–350) in the context of constant vorticity. Very good agreement is found for a range of values of the vorticity.
Assessing food-based strategies to address anaemia in pregnancy in rural plains Nepal: a mixed methods study
Authors: Morrison Joanna , Giri Romi , James Philip , Arjyal Abriti , Kharel Chandani , Saville Naomi , Baral Sushil , Hillman Sara , Harris-Fry Helen
Published: October 2022

Anaemia in pregnancy is a persistent health problem in Nepal and could be reduced through nutrition counselling and strengthened iron folic acid supplementation programmes. We analysed 24-hour diet recall data from 846 pregnant women in rural plains Nepal, using linear programming to identify the potential for optimised food-based strategies to increase iron adequacy. We then conducted qualitative research to analyse how anaemia was defined and recognised, how families used food-based strategies to address anaemia, and the acceptability of optimised food-based strategies. We did 16 interviews of recently pregnant mothers, three focus group discussions with fathers, three focus group discussions with mothers-in-law and four interviews with key informants. Dietary analyses showed optimised diets did not achieve 100 % of recommended iron intakes, but iron intakes could be doubled by increasing intakes of green leaves, egg and meat. Families sought to address anaemia through food-based strategies but were often unable to because of the perceived expense of providing an ‘energy-giving’ diet. Some foods were avoided because of religious or cultural taboos, or because they were low status and could evoke social consequences if eaten. There is a need for counselling to offer affordable ways for families to optimise iron adequacy. The participation of communities in tailoring advice to ensure cultural relevance and alignment with local norms is necessary to enable its effectiveness.
Estimated polyphenol intake and major food sources of the Brazilian population: changes between 2008–2009 and 2017–2018
Authors: Carnauba Renata A. , Sarti Flavia M. , Hassimotto Neuza M. A. , Lajolo Franco M.
Published: October 2022

Assessing the dietary intake of polyphenols and their major food sources is the first step towards documenting the associations with health outcomes. Considering recent changes in dietary patterns of the Brazilian population, continuous monitoring of polyphenol intake is important. Thus, the present study was conducted to estimate the polyphenol intake and major food sources in the diet of the Brazilian population using data from the most recent National Dietary Survey (NDS, 2017–2018), to characterise the intake changes according to demographic characteristics and to compare the intake over the past decade in Brazil. Data from two cross-sectional population-based surveys were analyzed in the study. Trends in polyphenol intake and major food sources were estimated using food consumption data from NDS 2008–2009 (n 34 003) and 2017–2018 (n 46 164). The median (25–75th percentiles) of energy-adjusted polyphenol intake in 2017–2018 was 216·3 mg (125·3–495·2 mg) per 1000 kcal/d (4184 kJ/d), representing an increase of 12·3 mg/d from 2008–2009. However, unadjusted polyphenol intakes were similar between the surveys (medians: 364·3 mg/d in 2008–2009 and 366·9 mg/d in 2017–2018). The main food sources of total and polyphenol intake classes presented some variations between 2008–2009 and 2017–2018, with greater contribution of beans preparations, salads and tea to polyphenol intake, and decrease of orange contribution. Our study provided an updated information on polyphenol intake and its major food sources. The median intake remains lower than the reported by other populations. Furthermore, the results may contribute to future studies investigating temporal trends in polyphenol intake and disease risk.
A correspondence between inverse subsemigroups, open wide subgroupoids and cartan intermediate C*-subalgebras
Authors: Komura Fuyuta
Published: October 2022

For a given inverse semigroup action on a topological space, one can associate an étale groupoid. We prove that there exists a correspondence between the certain subsemigroups and the open wide subgroupoids in case that the action is strongly tight. Combining with the recent result of Brown et al., we obtain a correspondence between the certain subsemigroups of an inverse semigroup and the Cartan intermediate subalgebras of a groupoid C*-algebra.
DNA in nanochannels: theory and applications
Authors: Frykholm Karolin , Müller Vilhelm , KK Sriram , Dorfman Kevin D. , Westerlund Fredrik
Published: October 2022

Nanofluidic structures have over the last two decades emerged as a powerful platform for detailed analysis of DNA on the kilobase pair length scale. When DNA is confined to a nanochannel, the combination of excluded volume and DNA stiffness leads to the DNA being stretched to near its full contour length. Importantly, this stretching takes place at equilibrium, without any chemical modifications to the DNA. As a result, any DNA can be analyzed, such as DNA extracted from cells or circular DNA, and it is straight-forward to study reactions on the ends of linear DNA. In this comprehensive review, we first give a thorough description of the current understanding of the polymer physics of DNA and how that leads to stretching in nanochannels. We then describe how the versatility of nanofabrication can be used to design devices specifically tailored for the problem at hand, either by controlling the degree of confinement or enabling facile exchange of reagents to measure DNA–protein reaction kinetics. The remainder of the review focuses on two important applications of confining DNA in nanochannels. The first is optical DNA mapping, which provides the genomic sequence of intact DNA molecules in excess of 100 kilobase pairs in size, with kilobase pair resolution, through labeling strategies that are suitable for fluorescence microscopy. In this section, we highlight solutions to the technical aspects of genomic mapping, including the use of enzyme-based labeling and affinity-based labeling to produce the genomic maps, rather than recent applications in human genetics. The second is DNA–protein interactions, and several recent examples of such studies on DNA compaction, filamentous protein complexes, and reactions with DNA ends are presented. Taken together, these two applications demonstrate the power of DNA confinement and nanofluidics in genomics, molecular biology, and biophysics.
Learning words with unfamiliar orthography: The role of cognitive abilities
Authors: Bisson Marie-Josée
Published: October 2022

Research suggests new foreign language (FL) words are learned more easily if their phonology follows the phonotactic rules of the native language. Very little is known, however, about the impact of orthography on FL learning. This study investigated the cognitive mechanisms supporting the learning of words with familiar and unfamiliar orthographies. Participants took part in learning and meaning recall tasks, as well as a series of cognitive tasks (short-term and working memory tasks and tasks assessing their phonological and acoustic abilities). Orthographic and phonological familiarity judgments were collected using another sample of participants. Using a mixed-effects model, the results showed that orthographic familiarity impacted FL word learning even after controlling for phonological familiarity. However, there were no interactions with cognitive abilities.
We Must Always Pursue Economic Growth
Authors: Kogelmann Brian
Published: October 2022

Why pursue economic growth? For poor countries this is an easy question to answer, but it is more difficult for rich ones. Some of the world's greatest philosophers and economists – such as John Stuart Mill, John Maynard Keynes, and John Rawls – thought that, once a certain material standard of well-being has been achieved, economic growth should stop. I argue the opposite in this article. We always have reason to pursue economic growth. My argument is indirect. I shall not argue that economic growthitselfis always better. Rather, I shall argue thatstoppinggrowth requires morally objectionable actions. Economic growth tends to occur naturally if certain underlying conditions are in place. We have moral reasons to insist on these conditions independent their effect on growth, however. Halting growth requires that we alter these conditions, but we ought not do this.
Microbial Contamination of Groundwater Self‐Supply in Urban Indonesia: Assessment of Sanitary and Socio‐Economic Risk Factors
Authors: Genter F. , Putri G. L. , Pratama M. A. , Priadi C. , Willetts J. , Foster T.
Published: October 2022

In urban Indonesia, more than 40 million people rely on groundwater self‐supply, but the extent to which self‐supply delivers safe water and the associated risk factors for fecal contamination remain unclear. This study quantifiedEscherichia coli(E.coli) for 511 self‐supply sources and at point‐of‐use for 173 households in the Indonesian cities of Bekasi and Metro. A structured questionnaire collected information about the household, water sources, and potential contamination sources. Univariate and multivariate logistic regression analysis examined risk factors for fecal contamination.E.coliwas detected in 66% of sources, including 55% of boreholes, 64% of protected dug wells, and 82% of unprotected dug wells. Widespread boiling of water meant microbial quality improved significantly between source and point‐of‐use, withE.colidetected in 30% of self‐supply samples at point‐of‐use. Unprotected dug wells were significantly more likely to be contaminated than boreholes. In Bekasi, the analysis found a significant association between presence ofE.coliand sanitation systems located within 10 m of the groundwater source. In Metro, poorer households had significantly higher odds of contamination than wealthier households. Other significant factors included shallower borehole depths in Bekasi, use of a rope and bucket, and absence of a concrete platform in Metro. In Bekasi,E.coliconcentration at source was significantly associated with water quality at point‐of‐use. Risk of fecal contamination could be reduced by supporting households to invest in improved protection, and by facilitating promotion for safe household water treatment. Support for self‐supply improvements should be weighed against the expansion and improvement of piped water services.
Industrial Particulate Pollution and Historical Land Use Contribute Metals of Concern to Dust Deposited in Neighborhoods Along the Wasatch Front, UT, USA
Authors: Putman Annie L. , Jones Daniel K. , Blakowski Molly A. , DiViesti Destry , Hynek Scott A. , Fernandez Diego P. , Mendoza Daniel
Published: October 2022

The Salt Lake Valley, UT, USA, is proximal to the desiccating Great Salt Lake (GSL). Prior work has found that this lakebed/playa contributes metals‐laden dust to snow in the Wasatch and Uinta Mountains. Dust and industrial particulate pollution are also delivered to communities along the Wasatch Front, but their sources, compositions, and fluxes are poorly characterized. In this study, we analyzed the dust deposited in 18 passive samplers positioned near the GSL, in cities in and near the Salt Lake Valley for total dust flux, the <63 µm dust fraction, 87Sr/86Sr, and trace element geochemistry. We compared spatial patterns in metal flux and abundance with community‐level socioeconomic metrics. We observed the highest dust fluxes at sites near the GSL playa. Within the urban corridor, 87Sr/86Sr and trace element relative abundances suggest that most of the dust to which people are regularly exposed may be fugitive dust from local soil materials. The trace metal content of dust deposited along the Wasatch Front exceeded Environmental Protection Agency screening levels and exhibited enrichment relative to both the upper continental crust and the dust collected adjacent to GSL. Sources of metals to dust deposited along the Wasatch Front may include industrial activities like mining, oil refining, as well as past historical pesticide and herbicide applications. Arsenic and vanadium indicated a statistically significant positive correlation with income, whereas lead, thallium, and nickel exhibited higher concentrations in the least wealthy and least white neighborhoods.
Planet Size Controls Fe Isotope Fractionation Between Mantle and Core
Authors: Ni Peng , Shahar Anat , Badro James , Yang Jing , Bi Wenli , Zhao Jiyong , Hu Michael Y. , Alp Esen E.
Published: October 2022

As an element ubiquitous in the Solar system, the isotopic composition of iron exhibits rich variations in different planetary reservoirs. Such variations reflect the diverse range of differentiation and evolution processes experienced by their parent bodies. A key in deciphering iron isotope variations among planetary samples is to understand how iron isotopes fractionate during core formation. Here we report new Nuclear Resonant Inelastic X‐ray Scattering experiments on silicate glasses of bulk silicate Earth compositions to measure their force constants at high pressures of up to 30 GPa. The force constant results are subsequently used to constrain iron isotope fractionation during core formation on terrestrial planets. Using a model that integrates temperature, pressure, core composition, and redox state of the silicate mantle, we show that core formation might lead to an isotopically light mantle for small planetary bodies but a heavy one for Earth‐sized terrestrial planets.
Analysis of Turbulence Reports and ERA5 Turbulence Diagnostics in a Tropopause‐Based Vertical Framework
Authors: Kaluza T. , Kunkel D. , Hoor P.
Published: October 2022

In the tropopause region turbulence exhibits a common feature with posing a threat for aviation as well as presenting a pathway for cross tropopause exchange. However, current numerical weather prediction and in particular climate models still struggle to resolve a large part of the dynamics responsible for turbulence generation. This renders high resolution observations of turbulence to be very valuable to identify the spatio‐temporal distribution of turbulence. In this study we use aircraft observations along with reanalysis data over the North Atlantic during winter season to analyze turbulence occurrence. Using a tropopause‐based coordinate system, we found that turbulence occurs within a sharp unimodal distribution which maximizes just below the tropopause. Turbulence also significantly affects the first 2  km above the tropopause which highlights its potential impact on the formation of the so called extratropical mixing layer around the tropopause.
Seasonal‐Interannual Predictions of Summer Precipitation Over the Tibetan Plateau in North American Multimodel Ensemble
Authors: Wang Lin , Ren Hong‐Li , Xu Xiangde , Huang Bohua , Wu Jie , Liu Jingpeng
Published: October 2022

Variations of precipitation over the Tibetan Plateau (TP) have great hydrometeorological impacts on local and surrounding areas. Focusing on the TP precipitation in the boreal summer, this study investigates the seasonal‐interannual predictions of eight dynamical models from the North‐American Multi‐Model Ensemble (NMME) using different observational data sets for verification. Results show dynamical prediction skill of the TP precipitation is regionally dependent with significantly high skills in the southwestern TP up to about three‐season ahead. Prediction skill of precipitation anomalies over the southwestern TP is significantly reliant on the models' ability in reproducing the observed relationship between the anomalous southwest‐TP precipitation and Pacific Sea surface temperature (SST). Using the different gridded observational data sets as verifications can lead to variations in prediction skills, and the multi‐observation mean tends to obtain the highest skills over the southwestern TP. These results provide a deeper understanding of dynamical seasonal‐interannual predictability of summer precipitation in TP.
Geomagnetic Disturbances That Cause GICs: Investigating Their Interhemispheric Conjugacy and Control by IMF Orientation
Authors: Engebretson Mark J. , Simms Laura E. , Pilipenko Viacheslav A. , Bouayed Lilia , Moldwin Mark B. , Weygand James M. , Hartinger Michael D. , Xu Zhonghua , Clauer C. Robert , Coyle Shane , Willer Anna N. , Freeman Mervyn P. , Gerrard Andy J.
Published: October 2022

Nearly all studies of impulsive geomagnetic disturbances (GMDs, also known as magnetic perturbation events MPEs) that can produce dangerous geomagnetically induced currents (GICs) have used data from the northern hemisphere. In this study, we investigated GMD occurrences during the first 6 months of 2016 at four magnetically conjugate high latitude station pairs using data from the Greenland West Coast magnetometer chain and from Antarctic stations in the conjugate AAL‐PIP magnetometer chain. Events for statistical analysis and four case studies were selected from Greenland/AAL‐PIP data by detecting the presence of >6 nT/s derivatives of any component of the magnetic field at any of the station pairs. For case studies, these chains were supplemented by data from the BAS‐LPM chain in Antarctica as well as Pangnirtung and South Pole in order to extend longitudinal coverage to the west. Amplitude comparisons between hemispheres showed (a) a seasonal dependence (larger in the winter hemisphere), and (b) a dependence on the sign of the By component of the interplanetary magnetic field (IMF): GMDs were larger in the north (south) when IMF By was >0 (<0). A majority of events occurred nearly simultaneously (to within ±3 min) independent of the sign of By as long as |By| ≤ 2 |Bz|. As has been found in earlier studies, IMF Bz was <0 prior to most events. When IMF data from Geotail, Themis B, and/or Themis C in the near‐Earth solar wind were used to supplement the time‐shifted OMNI IMF data, the consistency of these IMF orientations was improved.
Middle Miocene Climate and Stable Oxygen Isotopes in Europe Based on Numerical Modeling
Authors: Botsyun Svetlana , Ehlers Todd A. , Koptev Alexander , Böhme Madelaine , Methner Katharina , Risi Camille , Stepanek Christian , Mutz Sebastian G. , Werner Martin , Boateng Daniel , Mulch Andreas
Published: October 2022

The Middle Miocene (15.99–11.65 Ma) of Europe witnessed major climatic, environmental, and vegetational change, yet we are lacking detailed reconstructions of Middle Miocene temperature and precipitation patterns over Europe. Here, we use a high‐resolution (∼0.75°) isotope‐enabled general circulation model (ECHAM5‐wiso) with time‐specific boundary conditions to investigate changes in temperature, precipitation, and δ18O in precipitation (δ18Op). Experiments were designed with variable elevation configurations of the European Alps and different atmospheric CO2 levels to examine the influence of Alpine elevation and global climate forcing on regional climate and δ18Op patterns. Modeling results are in agreement with available paleobotanical temperature data and with low‐resolution Middle Miocene experiments of the Miocene Model Intercomparison Project (MioMIP1). However, simulated precipitation rates are 300–500 mm/yr lower in the Middle Miocene than for pre‐industrial times for central Europe. This result is consistent with precipitation estimates from herpetological fossil assemblages, but contradicts precipitation estimates from paleobotanical data. We attribute the Middle Miocene precipitation change in Europe to shifts in large‐scale pressure patterns in the North Atlantic and over Europe and associated changes in wind direction and humidity. We suggest that global climate forcing contributed to a maximum δ18Op change of ∼2‰ over high elevation (Alps) and ∼1‰ over low elevation regions. In contrast, we observe a maximum modeled δ18Op decrease of 8‰ across the Alpine orogen due to Alpine topography. However, the elevation‐δ18Op lapse rate shallows in the Middle Miocene, leading to a possible underestimation of paleotopography when using present‐day δ18Op—elevation relationships data for stable isotope paleoaltimetry studies.
Impact of the COVID-19 pandemic on non-COVID-19 hospital mortality in patients with schizophrenia: a nationwide population-based cohort study
Authors: Boyer Laurent , Fond Guillaume , Pauly Vanessa , Orléans Veronica , Auquier Pascal , Solmi Marco , Correll Christoph U. , Yon Dong Keon , Llorca Pierre-Michel , Baumstarck-Barrau Karine , Duclos Antoine
Published: October 2022

It remains unknown to what degree resource prioritization toward SARS-CoV-2 (2019-nCoV) coronavirus (COVID-19) cases had disrupted usual acute care for non-COVID-19 patients, especially in the most vulnerable populations such as patients with schizophrenia. The objective was to establish whether the impact of the COVID-19 pandemic on non-COVID-19 hospital mortality and access to hospital care differed between patients with schizophrenia versus without severe mental disorder. We conducted a nationwide population-based cohort study of all non-COVID-19 acute hospitalizations in the pre-COVID-19 (March 1, 2019 through December 31, 2019) and COVID-19 (March 1, 2020 through December 31, 2020) periods in France. We divided the population into patients with schizophrenia and age/sex-matched patients without severe mental disorder (1:10). Using a difference-in-differences approach, we performed multivariate patient-level logistic regression models (adjusted odds ratio, aOR) with adjustment for complementary health insurance, smoking, alcohol and substance addiction, Charlson comorbidity score, origin of the patient, category of care, intensive care unit (ICU) care, major diagnosis groups and hospital characteristics. A total of 198,186 patients with schizophrenia were matched with 1,981,860 controls. The 90-day hospital mortality in patients with schizophrenia increased significantly more versus controls (aOR = 1.18; p < 0.001). This increased mortality was found for poisoning and injury (aOR = 1.26; p = 0.033), respiratory diseases (aOR = 1.19; p = 0.008) and for both surgery (aOR = 1.26; p = 0.008) and medical care settings (aOR = 1.16; p = 0.001). Significant changes in the case mix were noted with reduced admission in the ICU and for several somatic diseases including cancer, circulatory and digestive diseases and stroke for patients with schizophrenia compared to controls. These results suggest a greater deterioration in access to, effectiveness and safety of non-COVID-19 acute care in patients with schizophrenia compared to patients without severe mental disorders. These findings question hospitals’ resilience pertaining to patient safety and underline the importance of developing specific strategies for vulnerable patients in anticipation of future public health emergencies.
Deciphering transcriptome alterations in bone marrow hematopoiesis at single-cell resolution in immune thrombocytopenia
Authors: Liu Yan , Zuo Xinyi , Chen Peng , Hu Xiang , Sheng Zi , Liu Anli , Liu Qiang , Leng Shaoqiu , Zhang Xiaoyu , Li Xin , Wang Limei , Feng Qi , Li Chaoyang , Hou Ming , Chu Chong , Ma Shihui , Wang Shuwen , Peng Jun
Published: October 2022

Immune thrombocytopenia (ITP) is an autoimmune disorder, in which megakaryocyte dysfunction caused by an autoimmune reaction can lead to thrombocytopenia, although the underlying mechanisms remain unclear. Here, we performed single-cell transcriptome profiling of bone marrow CD34+ hematopoietic stem and progenitor cells (HSPCs) to determine defects in megakaryopoiesis in ITP. Gene expression, cell-cell interactions, and transcriptional regulatory networks varied in HSPCs of ITP, particularly in immune cell progenitors. Differentially expressed gene (DEG) analysis indicated that there was an impaired megakaryopoiesis of ITP. Flow cytometry confirmed that the number of CD9+ and HES1+ cells from Lin−CD34+CD45RA− HSPCs decreased in ITP. Liquid culture assays demonstrated that CD9+Lin−CD34+CD45RA− HSPCs tended to differentiate into megakaryocytes; however, this tendency was not observed in ITP patients and more erythrocytes were produced. The percentage of megakaryocytes differentiated from CD9+Lin−CD34+CD45RA− HSPCs was 3-fold higher than that of the CD9− counterparts from healthy controls (HCs), whereas, in ITP patients, the percentage decreased to only 1/4th of that in the HCs and was comparable to that from the CD9− HSPCs. Additionally, when co-cultured with pre-B cells from ITP patients, the differentiation of CD9+Lin−CD34+CD45RA− HSPCs toward the megakaryopoietic lineage was impaired. Further analysis revealed that megakaryocytic progenitors (MkP) can be divided into seven subclusters with different gene expression patterns and functions. The ITP-associated DEGs were MkP subtype-specific, with most DEGs concentrated in the subcluster possessing dual functions of immunomodulation and platelet generation. This study comprehensively dissects defective hematopoiesis and provides novel insights regarding the pathogenesis of ITP.
Cryptic and ubiquitous aplastidic cryptophytes are key freshwater flagellated bacterivores
Authors: Šimek Karel , Mukherjee Indranil , Szöke-Nagy Tiberiu , Haber Markus , Salcher Michaela M , Ghai Rohit
Published: October 2022

Morphology-based microscopic approaches are insufficient for a taxonomic classification of bacterivorous heterotrophic nanoflagellates (HNF) in aquatic environments since their cells do not display reliably distinguishable morphological features. This leads to a considerable lack of ecological insights into this large and taxonomically diverse functional guild. Here, we present a combination of fluorescence in situ hybridization followed by catalyzed reporter deposition (CARD-FISH) and environmental sequence analyses which revealed that morphologically indistinguishable, so far largely cryptic and uncultured aplastidic cryptophytes are ubiquitous and prominent protistan bacterivores in diverse freshwater ecosystems. Using a general probe for Cryptophyceae and its heterotrophic CRY1 lineage, we analyzed different water layers in 24 freshwater lakes spanning a broad range of trophic states, sizes and geographical locations. We show that bacterivorous aplastidic cryptophytes and the CRY1 lineage accounted for ca. 2/3 and ¼ of total HNF, respectively, in both epilimnetic and hypolimnetic samples. These heterotrophic cryptophytes were generally smaller and more abundant than their chloroplast-bearing counterparts. They had high uptake rates of bacteria, hinting at their important roles in channeling carbon flow from prokaryotes to higher trophic levels. The worldwide ubiquity of Cryptophyceae and its CRY1 lineage was supported by 18S rRNA gene sequence analyses across a diverse set of 297 freshwater metagenomes. While cryptophytes have been considered to be mainly plastidic “algae”, we show that it is the aplastidic counterparts that contribute considerably to bacterial mortality rates. Additionally, our results suggest an undiscovered diversity hidden amongst these abundant and morphologically diverse aplastidic cryptophytes.
Genetic and functional analyses implicate microRNA 499A in bipolar disorder development
Authors: Tielke Aileen , Martins Helena , Pelzl Michael A. , Maaser-Hecker Anna , David Friederike S. , Reinbold Céline S. , Streit Fabian , Sirignano Lea , Schwarz Markus , Vedder Helmut , Kammerer-Ciernioch Jutta , Albus Margot , Borrmann-Hassenbach Margitta , Hautzinger Martin , Hünten Karola , Degenhardt Franziska , Fischer Sascha B. , Beins Eva C. , Herms Stefan , Hoffmann Per , Schulze Thomas G. , Witt Stephanie H. , Rietschel Marcella , Cichon Sven , Nöthen Markus M. , Schratt Gerhard , Forstner Andreas J.
Published: October 2022

Bipolar disorder (BD) is a complex mood disorder with a strong genetic component. Recent studies suggest that microRNAs contribute to psychiatric disorder development. In BD, specific candidate microRNAs have been implicated, in particular miR-137, miR-499a, miR-708, miR-1908 and miR-2113. The aim of the present study was to determine the contribution of these five microRNAs to BD development. For this purpose, we performed: (i) gene-based tests of the five microRNA coding genes, using data from a large genome-wide association study of BD; (ii) gene-set analyses of predicted, brain-expressed target genes of the five microRNAs; (iii) resequencing of the five microRNA coding genes in 960 BD patients and 960 controls and (iv) in silico and functional studies for selected variants. Gene-based tests revealed a significant association with BD for MIR499A, MIR708, MIR1908 and MIR2113. Gene-set analyses revealed a significant enrichment of BD associations in the brain-expressed target genes of miR-137 and miR-499a-5p. Resequencing identified 32 distinct rare variants (minor allele frequency < 1%), all of which showed a non-significant numerical overrepresentation in BD patients compared to controls (p = 0.214). Seven rare variants were identified in the predicted stem-loop sequences of MIR499A and MIR2113. These included rs142927919 in MIR2113 (pnom = 0.331) and rs140486571 in MIR499A (pnom = 0.297). In silico analyses predicted that rs140486571 might alter the miR-499a secondary structure. Functional analyses showed that rs140486571 significantly affects miR-499a processing and expression. Our results suggest that MIR499A dysregulation might contribute to BD development. Further research is warranted to elucidate the contribution of the MIR499A regulated network to BD susceptibility.
Betaine promotes osteogenic differentiation in immortalized human dental pulp-derived cells
Authors: Kornsuthisopon Chatvadee , Nantanapiboon Dusit , Rochanavibhata Sunisa , Nowwarote Nunthawan , Namangkalakul Worachat , Osathanon Thanaphum
Published: October 2022

Objectives

This study aimed to evaluate the effect of betaine (BET) on immortalized human dental pulp stem cell (ihDP) osteogenic differentiation.

Materials and methods

hDPs were immortalized using SV40 T-antigen transfection. Characterization, multilineage differentiation, proliferation, cell cycle, colony-forming unit, and cellular senescence were evaluated (n = 4). The effect of BET on ihDP response was assessed (n = 4). Osteogenic differentiation was detected using ALP, ARS staining, and RT-qPCR (n = 4). To investigate the involvement of calcium signaling, the cells were pretreated with either 8-(NN-diethylamino)octyl-3,4,5-trimethoxybenzoate (TMB-8) or thapsigargin before BET treatment (n = 6).

Results

ihDPs retained similar phenotypic characteristics presented in hDPs but exhibited an increase in cell proliferation and extended culture to passage 25. An increased proportion of cells in S and G2/M phases without senescence was observed in ihDPs. BET (50 mM) treatment significantly increased mineral deposition at 14 days and upregulated ALP, MSX2, BMP2, and RUNX2 expression. TMB-8 pretreatment reduced the effect of BET-induced ihDP osteogenic differentiation, whereas thapsigargin promoted osteogenic differentiation in ihDPs synergistically with BET.

Conclusion

ihDPs showed superior proliferation ability and a longer life span, which could serve as a promising cell for regenerative dentistry. BET promoted odonto/osteogenic differentiation via intracellular calcium regulation.
Does the pursuit of scientific excellence serve or hamper translational medical research: an historical perspective from hematological malignancies
Authors: Bunce Chris M. , Khanim Farhat L. , Drayson Mark T.
Published: October 2022

Despite enormous global investment, translational medical research faces considerable challenges and patients, and their doctors are frequently frustrated by the apparent lack of research activity or progress. Understanding the factors that prevent innovative research discoveries from making it to clinical trials is a multifaceted problem. However, one question that must be addressed is whether the nature of current research activity and the factors that influence the conduct of pre-clinical research, permit, or hamper the timely progression of laboratory-based observations to proof of concept (PoC) clinical trials. Inherent in this question is to what extent a deep mechanistic understanding of a potential new therapy is required before commencing PoC studies, and whether patients are better served when mechanistic and clinical studies progress side by side rather than in a more linear fashion. Here we address these questions by revisiting the historical development of hugely impactful and paradigm-changing innovations in the treatment of hematological cancers. First, we compare the history and route to clinical PoC, of two molecularly-targeted therapies that are BCR:ABL inhibitors in chronic myeloid leukaemia and all-trans retinoic acid (ATRA) in acute promyelocytic leukaemia (APL). We then discuss the history of arsenic trioxide as additional APL therapy, and the repurposing of thalidomide as effective multiple myeloma therapy. These stories have surprising elements of commonality that demand debate about the modern-day hard and soft governance of medical research and whether these processes appropriately align the priorities of advancing scientific knowledge and the need of patients.
Relationship between dietary intake and erythrocyte PUFA in adolescents from a Western Australian cohort
Authors: Wan Fuzhen , Pan Feng , Mori Trevor A. , O’Sullivan Therese A. , Beilin Lawrence J. , Oddy Wendy H.
Published: October 2022

Background

Population-based studies show that the intake of omega-3 (n-3) and omega-6 (n-6) polyunsaturated fatty acids (PUFA) are associated with a range of health conditions. Therefore, the reliability of food frequency questionnaires (FFQ) as rapid and easily accessible screening tools for PUFA intake deserve investigation.

Objective

We aimed to assess the relationship between erythrocyte fatty acids and fatty acid intake collected using the Commonwealth Scientific and Industrial Research Organisation (CSIRO) food frequency questionnaire in an adolescent cohort.

Design

A cross-sectional study using data from 1155 young adolescents participating in the 14-year follow-up of the Raine Study. Bland–Altman plots were used to determine the agreement between dietary intake and erythrocyte levels of each fatty acid.

Results

The main dietary source of n-3 long-chain (LC) PUFA was ‘fresh fish’ (53% of total n-3 LC-PUFA). Docosahexaenoic acid (DHA) showed the strongest correlation between erythrocyte and diet assessment (r = 0.274; p < 0.001), whilst linoleic acid (LA) (r = 0.103; p < 0.001) and arachidonic acid (AA) (r = −0.06; p = 0.042) showed weaker correlations, with limits of agreement relatively narrow. Bland–Altman plots showed a dose-dependent bias between the FFQ fatty acid data and corresponding erythrocyte data.

Conclusions

For the major n-3 and n-6 PUFA, dietary intakes derived from the FFQ showed weaker correlations and poorer agreement with erythrocyte levels, and the deviation between the two increased with higher intake levels.