bluuebunny/crossref_metadata_2025 huggingface dataset:
Never let a serious crisis go to waste: the introduction of supplemental carbon taxes in Europe
Authors: Bothner Fabio , Schrader Svenja Marie , Bandau Frank , Holzhauser Nicole
Published: January 2022

The literature on carbon pricing offers competing explanations for the introduction of carbon taxation. This article contributes to the field by highlighting the interaction of dynamic political factors and external pressures in explaining the timing of the adoption of carbon taxes. Focusing on the second wave of European countries, the study combines the multiple streams framework with qualitative comparative analysis to identify conditions favourable to the introduction of carbon taxes. Additional case studies on Ireland and Portugal serve to illuminate the reform process, especially the role of policy entrepreneurs. This approach yields three insights. First, fiscal crises provide political actors with an opportunity to raise environmental taxes. Second, the introduction of carbon taxation is most likely when push and pull factors come together, i.e. when high problem pressure coincides with governments receptive to environmental issues. Finally, the prospects of “green” policy entrepreneurs are strongly determined by their standing within the government.
Understanding innovation of health technology assessment methods: the IHTAM framework
Authors: Jiu Li , Hogervorst Milou A. , Vreman Rick A. , Mantel-Teeuwisse Aukje K. , Goettsch Wim G.
Published: January 2022

Adequate methods are urgently needed to guarantee the good practice of health technology assessment (HTA) for technologies with novel properties. The aim of the study was to construct a conceptual framework to help understand the innovation of HTA methods (IHTAM). The construction of the IHTAM framework was based on two scoping reviews, one on the current practice of innovating methods, that is existing HTA frameworks, and one on theoretical foundations for innovating methods outside the HTA discipline. Both aimed to identify and synthesize concepts of innovation (i.e., innovation processes and roles of stakeholders in innovation). Using these concepts, the framework was developed in iterative brainstorming sessions and subsequent discussions with representatives from various stakeholder groups. The framework was constructed based on twenty documents on innovating HTA frameworks and fourteen guidelines from three scientific disciplines. It includes a generic innovation process consisting of three phases (“Identification,” “Development,” and “Implementation”) and nine subphases. In the framework, three roles that HTA stakeholders can play in innovation (“Developers,” “Practitioners,” and “Beneficiaries”) are defined, and a process on how the stakeholders innovate HTA methods is included. The IHTAM framework visualizes systematically which elements and stakeholders are important to the development and implementation of novel HTA methods. The framework could be used by all stakeholders involved in HTA innovation to learn how to engage dynamically and collaborate effectively throughout the innovation process. HTA stakeholders in practice have welcomed the framework, though additional testing of its applicability and acceptance is essential.
The End Days of the Fourth Eelam War: Sri Lanka's Denialist Challenge to the Laws of War
Authors: Price Megan
Published: January 2022

During the final months of Sri Lanka's 2006–2009 civil war, Sri Lankan armed forces engaged in a disproportionate and indiscriminate shelling campaign against the Liberation Tigers of Tamil Eelam (LTTE), which culminated in the deaths of tens of thousands of civilians. Conventional wisdom suggests that Sri Lanka undermined international humanitarian law (IHL). Significantly, however, the Sri Lankan government did not directly challenge such law or attempt to justify its departure from it. Rather, it invented a new set of facts about its conduct to sidestep its legal obligations. Though indirect, this challenge was no less significant than had Sri Lanka explicitly rejected those obligations. Drawing on Clark et al.'s concept of denialism, this article details the nature of Sri Lanka's challenge to the standing of IHL. At the core of its denialist move, Sri Lanka maintained that while the LTTE was using civilians as human shields, government forces were adhering to a zero civilian casualty approach. With this claim, Sri Lanka absolved itself of any responsibility for the toll inflicted on civilians and sealed its conduct off from the ambit of IHL. This case illustrates how actors can considerably undermine the law using strategies of contestation far more subtle than direct confrontation.
Acceptance and challenges of the introduction of the routine community-based vitamin A supplementation strategy: the case of Burkina Faso
Authors: Ouédraogo Ousmane , Zeba Augustin Nawidimbasba , Kaboré Saidou , Berthé Abdramane , Drabo Koiné Maxime , Ouaro Dabiré Dowrot Bertine , Bambara Estelle , Ouédraogo Helene , Ilboudo Tegawendé Pierre , Konaté Claudine , Garnier Denis , Boussery Gunter , Kiburente Mediatrice , Zagré Noël Marie
Published: January 2022

Objectives:

With the phase-out of the polio campaigns, Burkina Faso has developed a new strategy for routine community-based vitamin A supplementation (VAS) by institutionalising community-based health workers (CBHW) to sustain the gain of two decades of successful programming. Formative research was conducted soon after the strategy was introduced to solicit feedback on the acceptability of the new approach by the implementing actors while identifying the main implementation challenges for improving its effectiveness and sustainability.

Design:

This qualitative study was conducted in 2018 through (i) document review, (ii) individual interviews with key informants at the central, regional and district levels, and (iii) focus groups with CBHW and caregivers.

Setting:

Data collection was carried out at six levels of sites covering the entire country and selected based on VAS coverage rates with the community routine. A total of six health districts were selected.

Participants:

We conducted 46 individual interviews with health workers and 20 focus groups with 59 CBHW and 108 caregivers.

Results:

The study showed good acceptability of the strategy by all stakeholders. In the first 2 years of implementation, the national coverage of VAS was maintained at a high level (above 90 %) and there was a reduction in operational costs. The main challenges included delayed CBHW remuneration and weak communication and supervision

Conclusions:

The acceptability of the community-based routine VAS was good and was perceived to have a high potential for sustainability. Addressing identified challenges will allow us to better manage the expectations of community stakeholders and maintain the initial results
Physical and chemical mechanisms that impact the detection, identification, and quantification of organic matter and the survival of microorganisms on the Martian surface – a review
Authors: Bak Ebbe Norskov , Nørnberg Per , Jensen Svend J. Knak , Thøgersen Jan , Finster Kai
Published: January 2022

The iconic Viking Landers that landed on Mars in 1976 demonstrated that the Martian surface is an extreme place, dominated by high UV fluxes and regolith chemistry capable of oxidizing organic molecules. From follow-on missions, we have learned that Mars was much warmer and wetter in its early history, and even some areas of Mars (such as crater lakes, possibly with sustained hydrothermal activity) were habitable places (e.g. Grotzinger et al. (2014). Science (New York, N.Y.) 343; Mangold et al. (2021). Science (New York, N.Y.). However, based on the Viking results we have learnt that the search for life and its remains is challenged by abiotic breakdown and alteration of organic material. In particular, the harsh radiation climate at the Martian surface that directly and indirectly could degrade organics has been held accountable for the lack of organics in the Martian regolith. Recent work simulating wind-driven erosion of basalts under Mars-like conditions has shown that this process, comparable to UV- and ionizing radiation, produces reactive compounds, kills microbes and removes methane from the atmosphere. and thereby could equally jeopardize the success of life-seeking missions to Mars. In this review, we summarize and discuss previous work on the role of physical and chemical mechanisms that affect the persistence of organics, and their consequences for the detection of life and/or its signatures in the Martian regolith and in the atmosphere.
Perceptions of Macro- and Micro-Level Factors Predict COVID-19 Self-Reported Health and Safety Guidelines Adherence
Authors: Lavallee Kristen L. , Brailovskaia Julia , Scholten Saskia , Schneider Silvia , Margraf Jürgen
Published: January 2022

Abstract. Introduction: Adherence to Covid-19 safety measures reduces the spread of the pathogen and lowers mortality rates. The present study examines microlevel (including sociodemographics, health risk factors, and mental health) and perceived macrolevel variables (including freedom, justice, and wealth) concerning self-perceived and self-reported Covid-19 safety measure adherence across eight countries. Methods: Self-reported adherence to Covid-19 safety measures and its potential predictors were assessed in representative samples from eight countries (total N = 7,437; Germany, France, Spain, Poland, Russia, Sweden, UK, US) by online surveys (end of May 2020 to the beginning of June 2020). Results: Self-reported adherence was positively predicted by female sex, higher age, higher social status, belonging to a Covid-19 risk group, being personally affected (physically, economically, and mentally), and positive mental health. Adherence was negatively predicted by depression and anxiety. Perceptions of governmental communication as credible and honest, government communication being guided by political interests, the feeling of being well informed, and perceived country-level freedom positively predicted self-reported adherence. Perceived country-level justice negatively predicted adherence, and perceived country-wide wealth was unrelated to it. Conclusions: Self-reported adherence to COVID-19 safety protocols is negatively predicted by depression, anxiety, and perceived justice, is positively predicted by perceived freedom, and not predicted by perceived country-level wealth.
Explicit Calculations of Wet‐Bulb Globe Temperature Compared With Approximations and Why It Matters for Labor Productivity
Authors: Kong Qinqin , Huber Matthew
Published: January 2022

Wet‐bulb globe temperature (WBGT) is a widely applied heat stress index. However, most applications of WBGT within the heat stress impact literature that do not use WBGT at all, but use one of the ad hoc approximations, typically the simplified WBGT (sWBGT) or the environmental stress index (ESI). Surprisingly, little is known about how well these approximations work for the global climate and climate change settings that they are being applied to. Here, we assess the bias distribution as a function of temperature, humidity, wind speed, and radiative conditions of both sWBGT and ESI relative to a well‐validated, explicit physical model for WBGT developed by Liljegren, within an idealized context and the more realistic setting of ERA5 reanalysis data. sWBGT greatly overestimates heat stress in hot‐humid areas. ESI has much smaller biases in the range of standard climatological conditions. Over subtropical dry regions, both metrics can substantially underestimate extreme heat. We show systematic overestimation of labor loss by sWBGT over much of the world today. We recommend discontinuing the use of sWBGT. ESI may be acceptable for assessing average heat stress or integrated impact over a long period like a year, but less suitable for health applications, extreme heat stress analysis, or as an operational index for heat warning, heatwave forecasting, or guiding activity modification at the workplace. Nevertheless, Liljegren's approach should be preferred over these ad hoc approximations and we provide a fast Python implementation to encourage its widespread use.
Interseismic Strain Accumulation Across the Main Recent Fault, SW Iran, From Sentinel‐1 InSAR Observations
Authors: Watson Andrew R. , Elliott John R. , Walters Richard J.
Published: January 2022

The Main Recent Fault is a major right‐lateral strike‐slip fault in the western Zagros mountains of Iran. Recent geodetic and geological studies estimate a low slip rate of 1–6 mm/yr at an unknown depth which, when combined with a non‐ideal fault geometry, makes the Main Recent Fault a difficult but interesting target for InSAR analysis. This analysis would further cement the estimated slip rate and provide an opportunity of estimate the depth to the base of the locked seismogenic zone, both important constraints on the seismic hazard posed by the fault, as well as for understanding how oblique convergence is accommodated and partitioned across the Zagros. We use 200 Sentinel‐1 SAR images from the past 5 years, spanning two ascending and two descending tracks, to estimate the first InSAR‐derived slip rate and locking depth for a 300 km long section of the fault. We utilize two established processing systems, LiCSAR and LiCSBAS, to produce interferograms and perform time series analysis, respectively. We constrain north‐south motion using GNSS observations, decompose our InSAR line‐of‐sight velocities into fault‐parallel and vertical motion, and fit 1‐D screw dislocation models to three fault‐perpendicular profiles of fault‐parallel velocity, following a Bayesian approach to estimate the posterior probability distribution on the fault parameters. We estimate an interseismic slip velocity of 2.4 ± 1.2 mm/yr below a loosely constrained 14 km locking depth, the first such estimate for the fault, and discuss the challenges in constraining the locking depth for low magnitude interseismic signals.
A Spatial Analysis of Dispersion Mechanisms in the Hydrological Response Using a Spatially Distributed Travel Time Model
Authors: Chong Pablo , Gironás Jorge , Niemann Jeffrey D.
Published: January 2022

Various dispersion mechanisms are known to link the spatial heterogeneity of the basin morphology and flow dynamics to the hydrologic response. Recent studies have conducted spatial analysis of the kinematic and geomorphological dispersion coefficients that characterize these mechanisms, as well as identified the influence of hillslopes, channels, and runoff production on their values. Nevertheless, an explicit and distributed dynamic representation of the travel times has not been used for this purpose. This study quantifies dispersion mechanisms by calculating spatially distributed flood wave travel times and hillslope and channel velocities, with a spatially distributed kinematic‐wave based model that explicitly accounts for the path heterogeneity, the dynamics of upstream flow contributions, and the nonlinear dependence on runoff intensity. Hence, the role of these factors and their influence on the dispersion mechanisms across different scales is studied in detail. Using different runoff intensities, the scaling of the dispersion mechanism coefficients according to the contributing areas within the Quintero Creek basin and two of its sub‐basins (in central Chile) is obtained. These scaling relationships are compared against those previously reported in the literature, which were obtained with approaches that simplify the treatment of travel times. Both basin‐specific and more general factors manifesting in the behavior of the dispersion mechanisms are found. Dispersion coefficients increase with area, and the role of the hillslope‐channel transition is controlled by runoff intensity, affecting the relative contribution of the dispersion mechanisms to the total dispersion at different spatial scales.
A simple additive staging system for newly diagnosed multiple myeloma
Authors: Abdallah Nadine H. , Binder Moritz , Rajkumar S. Vincent , Greipp Patricia T. , Kapoor Prashant , Dispenzieri Angela , Gertz Morie A. , Baughn Linda B. , Lacy Martha Q. , Hayman Suzanne R. , Buadi Francis K. , Dingli David , Go Ronald S. , Hwa Yi L. , Fonder Amie L. , Hobbs Miriam A. , Lin Yi , Leung Nelson , Kourelis Taxiarchis , Warsame Rahma , Siddiqui Mustaqeem A. , Kyle Robert A. , Bergsagel P. Leif , Fonseca Rafael , Ketterling Rhett P. , Kumar Shaji K.
Published: January 2022

Risk stratification in multiple myeloma is important for prognostication, patient selection for clinical trials, and comparison of treatment approaches. We developed and validated a staging system that incorporates additional FISH abnormalities not included in the R-ISS and reflects the additive effects of co-occurring high-risk disease features. We first evaluated the prognostic value of predefined cytogenetic and laboratory abnormalities in 2556 Mayo Clinic patients diagnosed between February 2004 and June 2019. We then used data from 1327 patients to develop a risk stratification model and validated this in 502 patients enrolled in the MMRF CoMMpass study. On multivariate analysis, high-risk IgH translocations [risk ratio (RR): 1.7], 1q gain/amplification (RR: 1.4), chromosome17 abnormalities (RR: 1.6), ISS III (RR: 1.7), and elevated LDH (RR: 1.3) were independently associated with decreased overall survival (OS). Among 1327 evaluable patients, OS was 11.0 (95% CI: 9.2–12.6), 7.0 (95% CI: 6.3–9.2), and 4.5 (95% CI: 3.7–5.2) years in patients with 0 (stage I), 1 (stage II), and ≥2 (stage III) high-risk factors, respectively. In the MMRF cohort, median OS was 7.8 (95% CI: NR-NR), 6.0 (95% CI: 5.7-NR), and 4.3 (95% CI: 2.7-NR) years in the 3 groups, respectively (P < 0.001). This 5-factor, 3-tier system is easy to implement in practice and improves upon the current R-ISS.
SpermTree, a species-level database of sperm morphology spanning the animal tree of life
Authors: Fitzpatrick John L. , Kahrl Ariel F. , Snook Rhonda R.
Published: January 2022

Sperm are the most morphologically variable cell type known, despite performing the same functional role of fertilizing eggs across all sexually reproducing species. Sperm morphology commonly varies among individuals, populations, closely related species, and across animal phyla. Sperm morphology has long been used as a tool for placing species in a phylogenetic context and a range of selective forces are hypothesized to influence sperm evolution and diversification. However, we currently lack robust examinations of macroevolutionary (i.e. across phyla) patterns of sperm evolution, due largely to the challenges of comparing sperm morphological data across the animal tree of life. Here we describe the SpermTree database, which currently represents 5,675 morphological descriptions of sperm morphology from 4,705 unique species from 27 animal phyla. This dataset includes measurements of sperm head, midpiece, flagellum and total length, the latter of which spans four orders of magnitude. All entries in the dataset are matched to currently accepted scientific names in taxonomic databases, facilitating the use of these data in analyses examining sperm evolution in animals.
Photosensitization agents for fs laser writing in PDMS
Authors: Boisvert Jean-Sebastien , Hlil Antsar , Loranger Sebastien , Riaz Ali , Ledemi Yannick , Messaddeq Younes , Kashyap Raman
Published: January 2022

This study aims at identifying compounds incorporated into Polydimethylsiloxane (PDMS) which produce large refractive index change under fs laser exposition, potentially leading to optimal writing of waveguides or photonic devices in such a soft host. Germanium derivative, titania and zirconite derivatives, benzophenone (Bp), irgacure-184/500/1173 and 2959 are investigated. We show a mapping of the RI index change relative to the writing speed (1 to 40 mm/s), the repetition rate (606 to 101 kHz) and the number of passes (1 to 8) from which we establish quantitative parameters to allow the comparison between samples. We show that the organic materials, especially irgacure-184 and benzophenone yield a significantly higher maximum refractive index change in the order of 10−2. We also show that the strongest photosensitivity is achieved with a mixture of organic/organo-metallic material of Bp + Ge. We report a synergetic effect on photosensitivity of this novel mixture.
Numerical analysis of a second-grade fuzzy hybrid nanofluid flow and heat transfer over a permeable stretching/shrinking sheet
Authors: Nadeem Muhammad , Siddique Imran , Awrejcewicz Jan , Bilal Muhammad
Published: January 2022

In this work, the heat transfer features and stagnation point flow of Magnetohydrodynamics (MHD) hybrid second-grade nanofluid through a convectively heated permeable shrinking/stretching sheet is reported. The purpose of the present investigation is to consider hybrid nanofluids comprising of Alumina $$\left( {{\text{Al}}_{{2}} {\text{O}}_{{3}} } \right)$$

Al
2

O
3

and Copper $$\left( {{\text{Cu}}} \right)$$

Cu

nanoparticles within the Sodium Alginate (SA) as a host fluid for boosting the heat transfer rate. Also, the effects of free convection, viscous dissipation, heat source/sink, and nonlinear thermal radiation are considered. The converted nonlinear coupled fuzzy differential equations (FDEs) with the help of triangular fuzzy numbers (TFNs) are solved using the numerical scheme bvp4c. The numerical results are acquired for various engineering parameters to study the Nusselt number, skin friction coefficient, velocity, and temperature distribution through figures and tables. For the validation, the current numerical results were found to be good as compared to existing results in limiting cases. It is also inspected by this work that with the enhancement of the volume fraction of nanoparticles, the heat transfer rate also increases. So, it may be taken as a fuzzy parameter for a better understanding of fuzzy variables. For the comparison, the volume fraction of nanofluids and hybrid nanofluid are said to be TFN [0, 0.1, 0.2]. In the end, we can see that fuzzy triangular membership functions (MFs) have not only helped to overcome the computational cost but also given better accuracy than the existent results. Finding from fuzzy MFs, the performance of hybrid nanofluids is better than nanofluids.
Comoclathrin, a novel potent skin-whitening agent produced by endophytic Comoclathris strains associated with Andalusia desert plants
Authors: Georgousaki Katerina , González-Menéndez Victor , Tormo José R. , Tsafantakis Nikolaos , Mackenzie Thomas A. , Martín Jesús , Gumeni Sentiljana , Trougakos Ioannis P. , Reyes Fernando , Fokialakis Nikolas , Genilloud Olga
Published: January 2022

As part of our screening program for the discovery of molecules of microbial origin with skin-whitening activity, 142 diverse fungal endophytes from a wide variety of Andalusia arid plants were screened, applying the OSMAC approach. The fungal strains CF-090361 and CF-090766, isolated from xerophytic plants, were selected as the most promising, while phylogenetic analysis revealed that both strains could represent a new species within the genus Comoclathris. The effect of different fermentation conditions on the production of tyrosinase inhibitory activity was examined, in order to identify the optimum cultivation conditions. LCMS based metabolomics was applied to determine significant differences between the strains and fermentation conditions, and to identify potential bioactive secondary metabolites. Bioassay-guided purification of the main active components led to the isolation of three new compounds (1–3), along with the known compounds graphostrin B (4) and brevianamide M (5). Compound 1 (Comoclathrin) demonstrated the strongest anti-tyrosinase activity (IC50 0.16 μΜ), which was 90-times higher than kojic acid (IC50 14.07 μΜ) used as positive control. Additionally, comoclathrin showed no significant cytotoxicity against a panel of cancer cell lines (HepG2, A2058, A549, MCF-7 and MIA PaCa-2) and normal BJ fibroblasts. These properties render comoclathrin an excellent development candidate as whitening agent.
Automated shape-transformable self-solar-tracking tessellated crystalline Si solar cells using in-situ shape-memory-alloy actuation
Authors: Yun Min Ju , Sim Yeon Hyang , Lee Dong Yoon , Cha Seung I.
Published: January 2022

Photovoltaic energy systems in urban situations need to achieve both high electricity production and high capacity in restricted installation areas. To maximize power output, solar-tracking systems tilt solar arrays to track the sun’s position, and typically flat modules are used to maximize the cross-sectional area. Such tracking systems are complex and expensive, and flat modules cannot utilize omnidirectional incident light. For solar systems in urban environments, we have developed two-dimensional (2D) or three-dimensional (3D) tessellated solar-cell modules that use shape transformation, and combine solar tracking and an arch structure for use in restricted areas. The modules can use scattered and omnidirectional incident light. Simply by attaching shape-memory alloy strips to the surface of the solar panels, the shape of the array can be transformed in response to heat from sunlight. Compared to a perfect solar-tracking system, our simulation results indicate that the modules present a large cross-sectional area perpendicular to the direction of sunlight and provide superior tracking performance, resulting in a 60% increase in electricity production over the course of 1 day. In addition, by using different designs for the tessellation units, dome shaped or other 3D structures are possible, for specific applications and to meet aesthetic requirements.
Boger nanofluid: significance of Coriolis and Lorentz forces on dynamics of rotating fluid subject to suction/injection via finite element simulation
Authors: Ali Bagh , Siddique Imran , Hussain Sajjad , Ali Liaqat , Baleanu Dumitru
Published: January 2022

This study briefings the roles of Coriolis, and Lorentz forces on the dynamics of rotating nanofluids flow toward a continuously stretching sheet. The nanoparticles are incorporated because of their unusual qualities like upgrade the thermal transportation, which are very important in heat exchangers, modern nanotechnology, electronics, and material sciences. The primary goal of this study is to improve heat transportation. Appropriate similarity transformations are applied for the principal PDEs to transform into nonlinear dimensionless PDEs. A widely recognized Numerical scheme known as the Finite Element Method is employed to solve the resultant convective boundary layer balances. Higher input in the solvent fraction parameter has a rising effect on the primary velocity and secondary velocity magnitude, and decreasing impact on the distributions of temperature. It is seen that growing contributions of the Coriolis, and Lorentz forces cause to moderate the primary and secondary velocities, but the temperature and concentration functions show opposite trend. The concentration, temperature, and velocities distributions for suction case is prominently than that of injection case, but inverse trend is observed for local Nusselt and Sherwood numbers. These examinations are relevant to the field of plastic films, crystal growing, paper production, heat exchanger, and bio-medicine.
Effects of endometriosis on immunity and mucosal microbial community dynamics in female olive baboons
Authors: Le Nhung , Cregger Melissa , Fazleabas Asgerally , Braundmeier-Fleming Andrea
Published: January 2022

Endometriosis is defined as the growth of endometrial tissue in ectopic locations, and is associated with altered immune and microbial phenotypes. It is unclear if these changes are the result of the disease or may be causative. We induced endometriosis in non-human primates (Papio Anubis) to test our hypothesis that the growth of endometriotic lesions results in alterations in immune and microbial dynamics that may advance disease progression. Baboon samples were collected pre-inoculation (prior to disease induction), at 3, 6, 9, and 15 months after disease induction. Tolerant regulatory T-cells (Tregs) and inflammatory T-helper 17 (Th17) cells were identified in peripheral blood and within the eutopic/ectopic endometrial tissues. Microbiome communities were identified in fecal/urine samples. The induction of endometriosis decreased peripheral Tregs cells while Th17 cells increased at all post-induction collections, thus reducing the Tregs:Th17 cells ratio, indicating systemic inflammation. Microbiome diversity and abundance were altered at each sample site after disease induction. Thus, induction of endometriosis in baboons caused an immune shift toward an inflammatory profile and altered mucosal microbial profiles, which may drive inflammation through production of inflammatory mediators. Immune and microbial profiling may lead to innovative diagnostic tools and novel therapies for endometriosis treatment.
Egg-laying increases body temperature to an annual maximum in a wild bird
Authors: Guillemette Magella , Pelletier David
Published: January 2022

Most birds, unlike reptiles, lay eggs successively to form a full clutch. During egg-laying, birds are highly secretive and prone to disturbance and predation. Using multisensor data loggers, we show that average daily body temperature during egg-laying is significantly increased (1 °C) in wild eider ducks (Somateria mollissima). Strikingly, this increase corresponds to the annual maximum body temperature (40.7 °C), representing a severe annual thermogenic challenge. This egg-laying-induced rise in body temperature may prove to be a common feature of wild birds and could be caused by habitat-related thermoregulatory adjustments and hormonal modulation of reproduction. We conclude our findings with new perspectives of the benefits of high body temperature associated with egg-laying of birds and the potential effect of heat stress that may occur with the future advent of heatwaves.
Detection of Mycobacterium tuberculosis multiple strains in sputum samples from patients with pulmonary tuberculosis in south western Uganda using MIRU-VNTR
Authors: Micheni Lisa Nkatha , Kassaza Kennedy , Kinyi Hellen , Ntulume Ibrahim , Bazira Joel
Published: January 2022

Infections with multiple strains of Mycobacterium tuberculosis are now widely recognized as a common occurrence. Identification of patients infected with multiple strains provides both insight into the disease dynamics and the epidemiology of tuberculosis. Analysis of Mycobacterial Interspersed Repetitive Unit-Variable-Number Tandem Repeats (MIRU-VNTR) has been shown to be highly sensitive in detecting multiple M. tuberculosis strains even in sputum. The goal of this study was to identify cases of multiple M. tuberculosis strain infections among patients diagnosed with pulmonary tuberculosis in Southwestern Uganda and assessment of factors associated with multiple strain infections. DNA extracted directly from 78 sputum samples, each from an individual patient, was analyzed using the standard 24 loci MIRU-VNTR typing. Five (6.4%) of the 78 patients were infected with multiple strains of M. tuberculosis with all of them being the newly diagnosed cases while two-thirds of them were co-infected with HIV. Exact regression analysis projected that the natives were more likely to harbor multiple strains (OR; 0.981, 95% CI 0–7.926) as well as those with a high microbial load (OR; 0.390, 95% CI 0–3.8167). Despite these findings being not statistically significant due to the small sample size, this points to a critical component of disease dynamics that has clinical implications and emphasizes a need for a study using a larger cohort. It is also essential to study the potential factors associated with higher risk of exposure to newly diagnosed and HIV positive patients at the community level. In addition, our ability to detect multiple M. tuberculosis strains using the standard 24 loci MIRU-VNTR typing especially with allelic diversity in loci 2059 and 3171, which are excluded from the 15-locus MIRU-VNTR, lead us to recommend the use of this genotyping technique, especially in areas with tuberculosis endemicity similar to this study.
Effect of endurance training and PGC-1α overexpression on calculated lactate production volume during exercise based on blood lactate concentration
Authors: Takeda Reo , Nonaka Yudai , Kakinoki Katsuyuki , Miura Shinji , Kano Yutaka , Hoshino Daisuke
Published: January 2022

Lactate production is an important clue for understanding metabolic and signal responses to exercise but its measurement is difficult. Therefore, this study aimed (1) to develop a method of calculating lactate production volume during exercise based on blood lactate concentration and compare the effects between endurance exercise training (EX) and PGC-1α overexpression (OE), (2) to elucidate which proteins and enzymes contribute to changes in lactate production due to EX and muscle PGC-1α OE, and (3) to elucidate the relationship between lactate production volume and signaling phosphorylations involved in mitochondrial biogenesis. EX and PGC-1α OE decreased muscle lactate production volume at the absolute same-intensity exercise, but only PGC-1α OE increased lactate production volume at the relative same-intensity exercise. Multiple linear regression revealed that phosphofructokinase, monocarboxylate transporter (MCT)1, MCT4, and citrate synthase equally contribute to the lactate production volume at high-intensity exercise within physiological adaptations, such as EX, not PGC-1α OE. We found that an exercise intensity-dependent increase in the lactate production volume was associated with a decrease in glycogen concentration and an increase in P-AMPK/T-AMPK. This suggested that the calculated lactate production volume was appropriate and reflected metabolic and signal responses but further modifications are needed for the translation to humans.
Construction and validation of a pyroptosis-related gene signature associated with the tumor microenvironment in uveal melanoma
Authors: Zhang Feng , Deng Yan , Wang Dong , Wang Shuai
Published: January 2022

The present study aimed to construct a pyroptosis-related gene signature in uveal melanoma (UM) patients. Patients from The Cancer Genome Atlas (TCGA) served as the training cohort, whereas patients (GSE22138) from Gene Expression Omnibus (GEO) served as the validation cohort. Using the Kaplan–Meier (KM) method, univariate analysis, and least absolute shrinkage and selection operator (LASSO) Cox regression, A five pyroptosis-related gene signature was constructed in the training cohort. Patients were divided into high- and low-risk groups. Survival analysis showed that patients in the high-risk group had a shorter survival time. Risk and survival analysis, time-independent receiver operating characteristic (ROC) curve analysis and principal component analysis (PCA) validated that the prognostic signature had greater predictive value in both cohorts. Multivariate analysis proved that the risk score was an independent prognostic factor. Functional analysis showed that the expressed genes in the high-risk group were most abundant in immunological repose-related and tumor-related signaling pathways. Single-sample gene-set enrichment analysis (ssGSEA) revealed that the different risk groups were associated with the tumor microenvironment. Moreover, the predictive signature could help patients be better matched to immunotherapy and targeted treatments. In conclusion, the pyroptosis-related gene signature associated with the tumor microenvironment maybe a reliable tool for predicting the prognosis of UM patients.
Livestock grazing impact differently on the functional diversity of dung beetles depending on the regional context in subtropical forests
Authors: Guerra Alonso Celeste B. , Zurita Gustavo A. , Bellocq M. Isabel
Published: January 2022

The replacement of native forest by cattle pastures reduces functional diversity; however, little is known about whether the changes depend on regional variation. Dung beetles are one of the most diverse and functionally important taxa; through organic matter burial, dung beetles improve soil quality. We collected dung beetles in native forests and cattle ranching areas in subtropical forests with contrasting climatic conditions: the Atlantic Forest, the Humid Chaco, and the Dry Chaco. We measured 11 traits related to the ecology and the physiology of species. Irrespectively of the region, functional richness was higher in forests (native and with cattle) when compared to open pastures. Humid forests (Atlantic Forest and Humid Chaco) showed higher functional richness than Dry Chaco. Functional dispersion in humid forests was similar between native forest and livestock systems, however, functional dispersion in the Dry Chaco was higher in open pastures compared to native forest. According to our results, native forests and forests with cattle maintain functional diversity in all regions. However, in the case of open pastures, the response depends on the regional context; the replacement of native forest by open pastures strongly affected functional diversity in humid forests and showed less impact on dry forest.
Induction of internal circadian desynchrony by misaligning zeitgebers
Authors: Heyde Isabel , Oster Henrik
Published: January 2022

24-h rhythms in physiology and behaviour are orchestrated by an endogenous circadian clock system. In mammals, these clocks are hierarchically organized with a master pacemaker residing in the hypothalamic suprachiasmatic nucleus (SCN). External time signals—so-called zeitgebers—align internal with geophysical time. During shift work, zeitgeber input conflicting with internal time induces circadian desynchrony which, in turn, promotes metabolic and psychiatric disorders. However, little is known about how internal desynchrony is expressed at the molecular level under chronodisruptive environmental conditions. We here investigated the effects of zeitgeber misalignment on circadian molecular organisation by combining 28-h light–dark (LD-28) cycles with either 24-h (FF-24) or 28-h feeding-fasting (FF-28) regimes in mice. We found that FF cycles showed strong effects on peripheral clocks, while having little effect on centrally coordinated activity rhythms. Systemic, i.e., across-tissue internal circadian desynchrony was profoundly induced within four days in LD-28/FF-24, while phase coherence between tissue clocks was maintained to a higher degree under LD-28/FF-28 conditions. In contrast, temporal coordination of clock gene activity across tissues was reduced under LD-28/FF-28 conditions compared to LD-28/FF-24. These results indicate that timed food intake may improve internal synchrony under disruptive zeitgeber conditions but may, at the same time, weaken clock function at the tissue level.
Molecular characterization of three CYP450 genes reveals their role in withanolides formation and defense in Withania somnifera, the Indian Ginseng
Authors: Shilpashree H. B. , Sudharshan S. J. , Shasany Ajit K. , Nagegowda Dinesh A.
Published: January 2022

The medicinal properties of Ashwagandha (Withania somnifera) are attributed to triterpenoid steroidal lactones, withanolides, which are proposed to be derived from phytosterol pathway, through the action of cytochrome P450 (CYP450) enzymes. Here, we report the characterization of three transcriptome-mined CYP450 genes (WsCYP749B1, WsCYP76 and WsCYP71B10), which exhibited induced expression in response to methyl jasmonate treatment indicating their role in secondary metabolism. All three WsCYP450s had the highest expression in leaf compared to other tissues. In planta characterization of WsCYP450s through virus induced gene silencing (VIGS) and transient overexpression approaches and subsequent metabolite analysis indicated differential modulation in the accumulation of certain withanolides in W. somnifera leaves. While WsCYP749B1-vigs significantly enhanced withaferin A (~ 450%) and reduced withanolide A (~ 50%), its overexpression drastically led to enhanced withanolide A (> 250%) and withanolide B (> 200%) levels and reduced 12-deoxywithastramonolide (~ 60%). Whereas WsCYP76-vigs led to reduced withanolide A (~ 60%) and its overexpression increased withanolide A (~ 150%) and reduced 12-deoxywithastramonolide (~ 60%). Silencing and overexpression of WsCYP71B10 resulted in significant reduction of withanolide B (~ 50%) and withanolide A (~ 60%), respectively. Further, while VIGS of WsCYP450s negatively affected the expression of pathogenesis-related (PR) genes and compromised tolerance to bacteria P. syringae DC3000, their overexpression in W. somnifera and transgenic tobacco led to improved tolerance to the bacteria. Overall, these results showed that the identified WsCYP450s have a role in one or several steps of withanolides biosynthetic pathway and are involved in conferring tolerance to biotic stress.
Visceral adipose tissue remodeling in pancreatic ductal adenocarcinoma cachexia: the role of activin A signaling
Authors: Xu Pauline C. , You Mikyoung , Yu Seok-Yeong , Luan Yi , Eldani Maya , Caffrey Thomas C. , Grandgenett Paul M. , O’Connell Kelly A. , Shukla Surendra K. , Kattamuri Chandramohan , Hollingsworth Michael A. , Singh Pankaj K. , Thompson Thomas B. , Chung Soonkyu , Kim So-Youn
Published: January 2022

Pancreatic ductal adenocarcinoma (PDAC) patients display distinct phenotypes of cachexia development, with either adipose tissue loss preceding skeletal muscle wasting or loss of only adipose tissue. Activin A levels were measured in serum and analyzed in tumor specimens of both a cohort of Stage IV PDAC patients and the genetically engineered KPC mouse model. Our data revealed that serum activin A levels were significantly elevated in Stage IV PDAC patients in comparison to age-matched non-cancer patients. Little is known about the role of activin A in adipose tissue wasting in the setting of PDAC cancer cachexia. We established a correlation between elevated activin A and remodeling of visceral adipose tissue. Atrophy and fibrosis of visceral adipose tissue was examined in omental adipose tissue of Stage IV PDAC patients and gonadal adipose tissue of an orthotopic mouse model of PDAC. Remarkably, white visceral adipose tissue from both PDAC patients and mice exhibited decreased adipocyte diameter and increased fibrotic deposition. Strikingly, expression of thermogenic marker UCP1 in visceral adipose tissues of PDAC patients and mice remained unchanged. Thus, we propose that activin A signaling could be relevant to the acceleration of visceral adipose tissue wasting in PDAC-associated cachexia.
Metabolomics study of COVID-19 patients in four different clinical stages
Authors: Valdés Alberto , Moreno Lorena Ortega , Rello Silvia Rojo , Orduña Antonio , Bernardo David , Cifuentes Alejandro
Published: January 2022

SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is the coronavirus strain causing the respiratory pandemic COVID-19 (coronavirus disease 2019). To understand the pathobiology of SARS-CoV-2 in humans it is necessary to unravel the metabolic changes that are produced in the individuals once the infection has taken place. The goal of this work is to provide new information about the altered biomolecule profile and with that the altered biological pathways of patients in different clinical situations due to SARS-CoV-2 infection. This is done via metabolomics using HPLC–QTOF–MS analysis of plasma samples at COVID-diagnose from a total of 145 adult patients, divided into different clinical stages based on their subsequent clinical outcome (25 negative controls (non-COVID); 28 positive patients with asymptomatic disease not requiring hospitalization; 27 positive patients with mild disease defined by a total time in hospital lower than 10 days; 36 positive patients with severe disease defined by a total time in hospital over 20 days and/or admission at the ICU; and 29 positive patients with fatal outcome or deceased). Moreover, follow up samples between 2 and 3 months after hospital discharge were also obtained from the hospitalized patients with mild prognosis. The final goal of this work is to provide biomarkers that can help to better understand how the COVID-19 illness evolves and to predict how a patient could progress based on the metabolites profile of plasma obtained at an early stage of the infection. In the present work, several metabolites were found as potential biomarkers to distinguish between the end-stage and the early-stage (or non-COVID) disease groups. These metabolites are mainly involved in the metabolism of carnitines, ketone bodies, fatty acids, lysophosphatidylcholines/phosphatidylcholines, tryptophan, bile acids and purines, but also omeprazole. In addition, the levels of several of these metabolites decreased to “normal” values at hospital discharge, suggesting some of them as early prognosis biomarkers in COVID-19 at diagnose.
Severity of thermal burn injury is associated with systemic neutrophil activation
Authors: Laggner Maria , Lingitz Marie-Therese , Copic Dragan , Direder Martin , Klas Katharina , Bormann Daniel , Gugerell Alfred , Moser Bernhard , Radtke Christine , Hacker Stefan , Mildner Michael , Ankersmit Hendrik Jan , Haider Thomas
Published: January 2022

Burn injuries elicit a unique and dynamic stress response which can lead to burn injury progression. Though neutrophils represent crucial players in the burn-induced immunological events, the dynamic secretion pattern and systemic levels of neutrophil-derived factors have not been investigated in detail so far. Serum levels of neutrophil elastase (NE), myeloperoxidase (MPO), citrullinated histone H3 (CitH3), and complement factor C3a were quantified in burn victims over 4 weeks post injury. Furthermore, the potential association with mortality, degree of burn injury, and inhalation trauma was evaluated. In addition, leukocyte, platelet, neutrophil, and lymphocyte counts were assessed. Lastly, we analyzed the association of neutrophil-derived factors with clinical severity scoring systems. Serum levels of NE, MPO, CitH3, and C3a were remarkably elevated in burn victims compared to healthy controls. Leukocyte and neutrophil counts were significantly increased on admission day and day 1, while relative lymphocytes were decreased in the first 7 days post burn trauma. Though neutrophil-derived factors did not predict mortality, patients suffering from 3rd degree burn injuries displayed increased CitH3 and NE levels. Accordingly, CitH3 and NE were elevated in cases with higher abbreviated burn severity indices (ABSI). Taken together, our data suggest a role for neutrophil activation and NETosis in burn injuries and burn injury progression. Targeting exacerbated neutrophil activation might represent a new therapeutic option for severe cases of burn injury.
Using Artificial Intelligence for Drug Repurposing
Authors: Bender A.
Published: January 2022

With more and more data being generated in the life sciences the application of computational algorithms and ‘Artificial Intelligence’ (AI) to various fields of drug discovery has also developed significantly in recent years. This chapter will firstly describe what is required for a computational algorithm to be able to be applied for drug repurposing, with a particular focus on the data available in the drug discovery/repurposing context, compared to that available in other domains. This section will be followed by an overview of methods and applications in the field and conclude by detailing which parts still need further development for AI in drug repurposing to have its maximum impact in the future.