bluuebunny/crossref_metadata_2025 huggingface dataset:
Degrees of Legitimacy
Authors: Brinkmann Matthias
Published: September 2024

It is increasingly common in the philosophical literature to claim that political legitimacy, normatively understood, comes in degrees. However, most authors fail to specify what talk of degrees means, and the notion remains opaque. Using the Hohfeld schema as a guide, I survey possible accounts, distinguishing them into “width”, “depth”, and “weight” proposals. I argue that each fails to provide a convincing account of scalar legitimacy. Thus, talk of degrees of legitimacy, as currently used, is in serious need of explanation.
Why Normative Behaviourism Does Not Improve Political Realism
Authors: Erman Eva , Möller Niklas
Published: September 2024

Focusing on ‘real actions’ of ‘real people’, normative behaviourism turns facts about observable patterns of behaviour into grounds for specific normative political principles. For this reason, this way of doing normative political theory has strong political realist credentials, given its methods, values and ambitions. In fact, according to its supporters, normative behaviourism is an improvement of political realism since it solves two problems that allegedly face many realists, namely, the ‘legitimacy problem’, i.e., how we should distinguish genuine acceptance of a political system from false acceptance, and ‘the institutional problem’, i.e., how we should translate political principles into viable political institutions. In this paper, we make two claims. First, normative behaviourism does not solve the legitimacy problem encountered by realists, because its solution rests on a flawed distinction between foundational principles and ‘principles that matter’, together with a problematic use of a Humean internal reasons approach. Second, normative behaviourism does not solve the institutional problem encountered by realists, because its solution is in fact much more unfeasible than realist prescriptions, since feasibility is interpreted as mere possibility. We wind up our analysis by showing that normative behaviourism encounters new problems that realist approaches typically do not face.
Ultrasound-guided kidney biopsy: a ten-year retrospective single-center experience and the promising role of clinical hypnosis
Authors: Angioi Andrea , Mascia Giacomo , Sirigu Danilo , Cao Riccardo , Bianco Paola , Onnis Daniela , Floris Matteo , Cabiddu Gianfranca , Pani Antonello , Lepori Nicola
Published: September 2024

This retrospective analysis investigates the outcomes and complications of 682 kidney biopsies performed at ARNAS G. Brotzu from 2010 to 2021. Our findings indicate a minor complication rate of 9.1%, with severe complications being exceedingly rare at 0.3%. Age did not contribute to an increased risk, underscoring the procedure’s safety across age groups. Clinical hypnosis was incorporated into the biopsy protocol in a subset of patients (n = 45) from April 2019 to December 2023. Over 90% of these patients reported no perception of the procedure, and 60% experienced no pain. According to STAY-Y test scores, this approach significantly reduced anxiety post-procedure (p = 0.001); no major or minor complications were observed in this group. While our study reaffirms the very low risk of severe complications in kidney biopsies, it also highlights the potential benefits of adjunct clinical hypnosis in enhancing patient comfort and cooperation during the procedure. This exploration opens a promising avenue for further investigation to improve patient experiences and procedural outcomes in kidney biopsies.
Mandibular device treatment in obstructive sleep apnea -A structured therapy adjustment considering night-to-night variability night-to-night variability in mandibular devices
Authors: Papenfuß Greta Sophie , König Inke R. , Hagen Christina , Frydrychowicz Alex , Zell Fenja , Ibbeken Alina Janna , Buzug Thorsten M. , Kirstein Ulrike , Kreft Lina , Grünberg Daniel , Hakim Samer , Steffen Armin
Published: September 2024

Background

Mandibular advancement devices (MAD) are a well-established treatment option for obstructive sleep apnea (OSA). MAD are considered preferably for patients with mild to moderate OSA presenting with a elevated night-to-night variability (NNV). This study aimed to determine the treatment effect of MAD on NNV considering different protrusion distances and patient related outcome (PRO).

Methods

We conducted a prospective cohort analysis of patients before MAD with 60% and 80% of the maximum protrusion. OSA severity was assessed using a home-sleep test for two consecutive nights. PRO contained the Epworth Sleepiness Scale (ESS) and sleep related quality of life (FOSQ).

Results

Twenty patients with a median overweight body-mass-index of 27.1 (interquartile range (IQR) 16.3 kg/m²), with a mainly mild to moderate OSA with an apnea -hypopnea index (AHI) of 18.3 / h (IQR 17.7) and elevated ESS of 12.5 (IQR 8.0) were included. As opposed to 80%, 60% protrusion significantly but not 80% relevantly reduced AHI (60%%: 11.2 (IQR 5.5)/h, p = 0.01; 80%: 12.9 (IQR18,0)/h, p = 0.32) and improved the ESS (60%: 8.0 (IQR 10,0); 80%: 10 (IQR 9.0)), with therapy settings. No correlation could be detected between NNV and ESS, and FOSQ changes. Higher baseline NNV was associated with severe OSA (p = 0.02) but not with gender, overweight, or status post-tonsillectomy.

Conclusions

OSA improvement is associated with lower NNV; both OSA and NNV are connected to the degree of protrusion. Therefore, higher NNV does not justify the exclusion of candidates for MAD treatment. PRO changes are not visibly affected by NNV but by general OSA changes. These findings may help to define and optimize future study designs for the primary outcome decision between objective OSA parameters and PRO.
Rearing conditions (isolated versus group rearing) affect rotenone-induced changes in the behavior of zebrafish (Danio rerio) embryos in the coiling assay
Authors: von Hellfeld Rebecca , Gade Christoph , Leist Marcel , Braunbeck Thomas
Published: September 2024

Under regulations such as REACH, testing of novel and established compounds for their (neuro)toxic potential is a legal requirement in many countries. These are largely based on animal-, cost-, and time-intensive in vivo models, not in line with the 3 Rs’ principle of animal experimentation. Thus, the development of alternative test methods has also received increasing attention in neurotoxicology. Such methods focus either on physiological alterations in brain development and neuronal pathways or on behavioral changes. An example of a behavioral developmental neurotoxicity (DNT) assay is the zebrafish (Danio rerio) embryo coiling assay, which quantifies effects of compounds on the development of spontaneous movement of zebrafish embryos. While the importance of embryo-to-embryo contact prior to hatching in response to environmental contaminants or natural threats has been documented for many other clutch-laying fish species, little is known about the relevance of intra-clutch contacts for zebrafish. Here, the model neurotoxin rotenone was used to assess the effect of grouped versus separate rearing of the embryos on the expression of the coiling behavior. Some group-reared embryos reacted with hyperactivity to the exposure, to an extent that could not be recorded effectively with the utilized software. Separately reared embryos showed reduced activity, compared with group-reared individuals when assessing. However, even the control group embryos of the separately reared cohort showed reduced activity, compared with group-reared controls. Rotenone could thus be confirmed to induce neurotoxic effects in zebrafish embryos, yet modifying one parameter in an otherwise well-established neurotoxicity assay such as the coiling assay may lead to changes in behavior influenced by the proximity between individual embryos. This indicates a complex dependence of the outcome of behavior assays on a multitude of environmental parameters.
Nucleotide metabolism in common bean pods during seed filling phase reveals the essential role of seed coats
Authors: Díaz-Baena Mercedes , Delgado-García Elena , deRave-Prieto Inés G. , Gálvez-Valdivieso Gregorio , Piedras Pedro
Published: September 2024

Common bean is a legume with high demand for human consumption and with high protein content on its seeds. The seed filling stage is a crucial step to obtain high-quality seeds with a good level of nutrients. For this, it is necessary for a correct communication between the different seed compartments. Nucleotides are essential components with nitrogen and phosphorous on its molecules, and its metabolism in seed development has not been studied in detail. In this manuscript, we have studied nucleotide metabolism in common bean pods during seed filling stage at pod valves, seed coats, and embryos. Nuclease and ribonuclease activities were assayed as nucleotide-generating enzymes, and nucleotidase, nucleosidase, and allantoinase as nucleotide-degrading activities. Nuclease was predominant in seed coats whereas ribonuclease was equally determined in seed coats and valves, although with differences in the three ribonucleases determined (16, 17, and 19 kDa). Nucleotidase and nucleosidase activities were detected in the three pods parts, and differently to nucleic degrading activities with significant activity in embryos. The relative expression of gene families coding for all these activities (S1 nuclease, S-like T2 ribonuclease, nucleotidase, nucleosidase and allantoinase) in the three pods parts was also studied. We have found the highest level of expression for some members of each family in seed coats. The allantoinase data suggest that nucleotide might be fully degraded in valves and seed coats but not in embryos. Overall, the data presented allow to conclude that there is an intense nucleotide metabolism in fruits during the seed filling stage with an especial involvement of seed coats in the process.
Post-lung transplant outcomes of connective tissue disease-related interstitial lung diseases compared with idiopathic interstitial pneumonia: a single-center experience in Japan
Authors: Yamaguchi Miho , Yamaya Takafumi , Kawashima Mitsuaki , Konoeda Chihiro , Kage Hidenori , Sato Masaaki
Published: September 2024

Objectives

The aim of this study was to investigate the outcomes of lung transplantation for connective tissue disease-related interstitial lung disease (CTD-ILD) conducted at our institution, compared with those for idiopathic interstitial pneumonias (IIPs).

Methods

We retrospectively reviewed patients with CTD-ILD and IIPs who underwent lung transplantation at our hospital from July 2015 to October 2023. We compared patients’ backgrounds, early complications within 28 days post-transplant (CTCAE grade 3 or higher), postoperative courses, and prognoses between the two groups.

Results

The CTD-ILD group (n = 19) and the IIPs group (n = 56) were compared. The CTD-ILD group had significantly higher preoperative use of corticosteroids and antifibrotic agents, mean pulmonary arterial pressure, anti-human leukocyte antigen antibody positivity, and donor age (p < 0.05). In addition, the CTD-ILD group had significantly longer operation times (579.0 vs 442.5 min), longer stays in the intensive care unit (17.0 vs 9.0 days) and hospital (58.0 vs 44.0 days); required more tracheostomies (57.9 vs 25.0%); and experienced more respiratory (52.6 vs 25.0%) and gastrointestinal (42.1 vs 8.9%) complications (p < 0.05). However, there were no significant differences in overall survival, nor chronic lung allograft dysfunction (CLAD)-free survival between the two groups.

Conclusion

Perioperative complications, notably respiratory and gastrointestinal complications, were prevalent after lung transplantation among CTD-ILD patients. Despite this, long-term survival rates were comparable to those observed in IIP cases.
Minimal *-varieties and superinvolutions
Authors: Di Vincenzo Onofrio M. , Nardozza Vincenzo C.
Published: September 2024

We introduce a class of finite-dimensional superalgebras over an algebraically closed field of characteristic zero, whose Grassmann envelopes generate all *-minimal varieties. Moreover, we prove that any affine minimal variety of superalgebras with superinvolution is generated by a suitable element in this selected class.
Development of a microfluidic SNP assay for lineage discrimination in the endangered hazel dormouse
Authors: Beez Tobias , Leyhausen Johanna , Mueller Sarah , von Thaden Alina , Bertolino Sandro , Büchner Sven , Fietz Joanna , Lang Johannes , Michaux Johan , Verbeylen Goedele , Nowak Carsten , Cocchiararo Berardino
Published: September 2024

The application of Genotyping-by-Sequencing (GBS) approaches is often restricted in wildlife monitoring and conservation genetics, as those fields often rely on noninvasively collected samples with low DNA content. Here we selected a subset of informative single-nucleotide polymorphisms (SNPs) from genome-wide data for lineage discrimination of a locally endangered Eurasian rodent, the hazel dormouse (Muscardinus avellanarius), and designed a microfluidic 96 SNP genotyping assay suitable for noninvasively collected samples. Analyses of 43 samples from different European countries confirmed successful discrimination of the Eastern and Western lineage and local substructure within those lineages, proving the suitability of the developed panel for identifying evolutionary significant units and conservation units. Application with 94 hair and scat samples collected in a recent monitoring study on the hazel dormouse in Southern Germany resulted in > 99.5% amplification success showing the applicability of the new tool in genetic wildlife monitoring and conservation studies.
Hemodynamic effect of supra-annular implantation of SAPIEN 3 balloon expandable valve
Authors: Yasuda Masakazu , Mizutani Kazuki , Onishi Kyohei , Onishi Naoko , Fujita Kosuke , Ueno Masafumi , Okamura Atsushi , Iwanaga Yoshitaka , Sakaguchi Genichi , Nakazawa Gaku
Published: September 2024

The hemodynamic impact of the implantation depth for balloon-expandable valves is under-investigated, especially with higher implantation techniques. We assessed the hemodynamic performance of supra-annular SAPIEN 3 valve implantation. This retrospective study involved consecutive patients who underwent transcatheter aortic valve replacement (TAVR) using the SAPIEN 3. The device implantation depth and transcatheter heart valve (THV) leaflet-nadir position were angiographically analyzed, and supra-annular implantation was defined as a higher leaflet-nadir position than the original annular line. The Doppler hemodynamic status was evaluated at patient discharge. Among 184 patients, 120 (65%) underwent supra-annular implantation, and their mean implantation depth was significantly lower than that of intra-annular implantation (1.1 vs. 5.2 mm, p < 0.001). No patients developed valve embolization or coronary occlusion, and none required the TAV-in-TAV procedure. Two (1.6%) patients in the supra-annular implantation group had a mild or greater paravalvular leak. Echocardiography demonstrated that supra-annular implantation had better hemodynamic performance, showing a larger indexed effective orifice area (iEOA) compared with intra-annular implantation (1.09 vs. 0.97 cm2/m2, p < 0.01). There was a weak but negative correlation between the implantation depth and iEOA (r =  − 0.27, p < 0.01). Moderate or severe prosthesis–patient mismatch (PPM) was found in 35.9% of the intra-annular group and 9.2% of supra-annular of the supra-annular group (p < 0.01). In the multivariable analysis, supra-annular implantation was an independent predictor of better THV function (iEOA > 0.85). Supra-annular SAPIEN 3 implantation provides beneficial hemodynamic effects and reduces the PPM risk.

Graphical abstract
DEM modelling of surface indentations caused by granular materials: application to wheel–rail sanding
Authors: Suhr Bettina , Skipper William A. , Lewis Roger , Six Klaus
Published: September 2024

The presented surface indentation model is one step towards building a DEM model for wheel–rail sanding. In railways, so-called low-adhesion conditions can cause problems in traction and braking, and sanding is used to overcome this problem. Sand grains are blasted towards wheel–rail contact, fracture repeatedly as they enter the nip and are drawn into the contact and then increase adhesion. Research on this topic has mostly been experimental, but focussed on adhesion enhancement measurement. Thus, physical mechanisms increasing the adhesion are not well understood. Previous works involved experiments and DEM modelling of single sand grain crushing tests under realistic wheel–rail contact pressures of 900 MPa, focusing on sand fragment spread and formation of clusters of solidified fragments. In the experiments, indents in the compressing steel plates were also observed, which are also observed on wheel and rail surfaces in railway operation. These are now modelled by adapting an existing surface indentation model from literature to the case of surface indentations caused by granular materials. Two test cases are studied, and experimental spherical indentation tests for model parametrisation are presented. In a proof of concept, the mentioned single sand grain crushing tests under 900 MPa pressure are simulated including the surface indentation model. This work contributes to DEM modelling of wheel–rail sanding, which is believed to be a good approach to deepen the understanding of adhesion increasing mechanisms under sanded conditions.
Identifying loci in mobility networks with applications in New Zealand work commutes: a statistical test for identifying extreme stationary distribution values in Markov transition matrices
Authors: Kane Michael J. , Gilani Owais , Khusainova Elena , Urbanek Simon
Published: September 2024

Human mobility describes physical patterns of movement of people within a spatial system. Many of these patterns, including daily commuting, are cyclic and quantifiable. These patterns capture physical phenomena tied to processes studied in urban planning, epidemiology, and other social, behavioral, and economic sciences. This paper advances human mobility research by proposing a statistical method for identifying locations that individual move to and through at a rate proportionally higher than other locations, using commuting data for the country of New Zealand as a case study. We term these locations mobility loci and they capture a global property of communities in which people commute. The method makes use of a directed-graph representation where vertices correspond to locations, and traffic between locations correspond to edge weights. Following a normalization, the graph can be regarded as a Markov chain whose stationary distribution can be calculated. The proposed permutation procedure is then applied to determine which stationary distribution values are larger than what would be expected, given the structure of the directed graph and traffic between locations. The results of this method are evaluated, including a comparison to what is already known about commuting patterns in the area as well as a comparison with similar features.
The Demand and Supply for Theatre: A Long-Run Analysis over the Italian Regions
Authors: Castiglione Concetta , Infante Davide
Published: September 2024

In Italy cultural policies are often set at national level without taking into account the dualism between the Northern and the Southern regions that exists in different social and economic sectors. Our aim is to fill this lacuna and to examine the Italian theatre market from both the demand and supply side considering the four Italian macro-areas. To this end, we apply both the seemingly unrelated regression and the three stage least square estimation techniques, to identify the factors influencing theatre demand and supply. The empirical analysis is conducted using a 35-year panel data (1980–2014) at country level (20 Italian regions) and separately for the four main areas (each of them including the related regions): North West, North East, Centre, and South and Islands. At the country level, the estimated results confirm as determinants of theatre demand, price and consumer income as well as complementary good (cinema), urban agglomeration and tourism flows. Theatre supply is influenced by past ticket price, income, past attendance, urban agglomeration and public subsidies. At regional level the results provide empirical support for the existence of a strong heterogeneity from both the demand and supply sides. We find that some of the variables that influence attendance and performances at national level play a different role at the local level hence cultural policies should take into account this heterogeneity.
Wer repräsentiert ‚das‘ Judentum im christlichen Religionsunterricht? Überlegungen zur didaktischen Reduktion und Gestaltung von Unterrichtsmaterialien
Authors: Willems Joachim , Dihle Ariane
Published: September 2024

Der vorliegende Beitrag beschäftigt sich mit der Darstellung des Judentums im christlichen (evangelischen, katholischen, konfessionell-kooperativen) Religionsunterricht. Ausgangspunkt ist die Frage, wer eine in sich heterogene Religion repräsentiert. Diese Frage muss aus Gründen der didaktischen Reduktion gestellt werden. Entsprechende didaktische Entscheidungen werden getroffen vor dem Hintergrund der einschlägigen fachdidaktischen Diskurse (hier vor allem des interreligiösen Lernens) und vielfältiger und wechselseitig aufeinander bezogener Konstruktionen von Selbst- und Fremdbildern; sie bewegen sich zudem immer in einem Feld unterschiedlicher Machtkonstellationen. Ausgehend von theoretischen Überlegungen und unter Rückgriff auf Schulbücher und weitere Unterrichtsmaterialien sowie Beispiele von innerjüdischen Debatten soll die Frage der Repräsentation grundlegend problematisiert werden. Abschließend werden Kriterien für eine didaktische Reduktion im Kontext der Frage nach der Repräsentation jüdischer Stimmen in einem christlichen Religionsunterricht entfaltet und diskutiert.
Communicating Effect Sizes to Teachers
Authors: Schneider Jürgen , Schmidt Kirstin , Bohrer Kristina , Merk Samuel
Published: September 2024

Abstract: This study explores how various visualizations impact teachers' understanding of effect sizes and their relevance to practice. In Study 1, 40 teachers assessed four visualization types displaying six effect sizes. Half-eye plots were perceived as less challenging and more informative compared to raincloud and Gardner–Altman plots. However, misconceptions of U3 and overlap were prevalent across all types. In Study 2, enrichment options (signaling, benchmarking) integrated into half-eye plots were examined for their impact on, among others, understanding and misconception reduction. While benchmarks increased time needed for decision-making, they did not improve accuracy compared to a control group and neither did signaling. However, both signaling options substantially reduced misconceptions. Furthermore, one signaling option increased participants' sensitivity to group differences. This study offers first indications of a promising visualization type, the half-eye plot, and an enrichment option to decrease misconceptions when considering visualization design in science communication efforts aimed at supporting educators.
Deterministic Model for Asteroid Thermal Evolution With Fragmentation and Reassembly Into a Gravitational Aggregate
Authors: Ren J. , Hesse M. A. , Dygert N. , Lucas M. P.
Published: September 2024

We present a model for the thermal evolution of asteroids that experience catastrophic fragmentation and reassembly into a gravitational aggregate. The three stage model comprises the initial radiogenic heating, fragmentation and cooling, and reassembly into a porous gravitational aggregate. The heat loss during catastrophic fragmentation is largely determined by the production of small particles that equilibrate thermally with ambient space. To determine this heat loss we combine a power‐law for the cumulative fragment mass distribution with analytic solutions for conductive cooling. To keep the model deterministic we fragment the parent body and reassemble the gravitational aggregate in shells ordered in decreasing volume. We use the resulting model to show that catastrophic fragmentation can lead to significant heat loss despite the short reassembly times (e.g., 1 year), due to the production of many small fragments. Despite the heat loss during fragmentation, the reassembled gravitational aggregate will retain more heat than the undisturbed parent body in the long term, due to the formation of an insulating megaregolith. Applied to the H‐chondrite parent body, our model can reproduce both the fast cooling rates at high temperatures and slow cooling rates at low temperature.
Variations in Rainfall Structure of Western North Pacific Landfalling Tropical Cyclones in the Warming Climates
Authors: Tran Thao Linh , Ritchie Elizabeth A. , Perkins‐Kirkpatrick Sarah E. , Bui Hai , Luong Thang M.
Published: September 2024

Observations and climate projections suggest a larger increase in tropical cyclone (TC)‐induced rainfall than that can be explained by the Clausius‐Clapeyron relationship of 7% increase in vapor content for each 1°C degree rise in temperature. However, these studies using diverse data sources and methods over various periods show inconsistencies regarding the location of this increase ‐ whether in the TC inner core or outer regions ‐ and offer differing explanations for the reported trends. This study uses the Pseudo‐global warming methodology on simulations of 117 western North Pacific TCs making landfall in Southeast Asia to investigate changes in TC rainfall structure by the end of the century under the SSP2‐4.5 and SSP3‐7.0 scenarios. Specifically, it tests the sensitivity of changing trends to various analysis methods used in previous studies and identifies the underlying physical mechanisms driving these changes. The findings indicate an amplified increase in rainfall in the TC inner core across all future scenarios, along with potentially decreased rainfall in the outer region under certain future climate conditions. Among TC categories, Supertyphoons exhibit the most significant increased rainfall across future states. Changes in TC primary and secondary circulations, TC structure, and the convergence of heat and moisture are the main factors shaping future rainfall patterns, outweighing the effects of changes in atmospheric and convective stability.
Deciphering the Prevalence of Warm‐Wet Extremes in Ice‐Covered Zones
Authors: Chen Xinlu , Xu Lianlian , Yang Ran , Cai Ming , Deng Yi , Chen Deliang , Yang Song , Liu Jiping , Yang Qinghua , Hu Xiaoming
Published: September 2024

Compound warm extremes exert profound impacts on environment, health, and socioeconomics. Yang et al. (2024) indicated a shift or transition from warm‐dry extremes (WDEs), common in non‐ice‐covered areas, to warm‐wet extremes (WWEs) in ice‐covered zones. Utilizing ERA5 reanalysis data, this study determined the duration and frequency of WDEs and WWEs across ice‐covered and non‐ice‐covered regions. A comprehensive analysis uncovers the physical mechanisms responsible for the paradigm differences and attributes them to the weakening of land‐atmosphere interaction caused by ice‐cover, which inhibits soil moisture feedback and reduces the intensity and duration of warm events in ice‐covered areas. Both WDEs and WWEs are associated with high‐pressure systems (HPs). WDEs, situated directly beneath HPs, intensify due to adiabatic warming from subsidence motions. Conversely, WWEs, located beneath the poleward fringes of HPs, emerge from advective warming and moistening associated with poleward intrusions of warm‐moist air.
Deoxygenation and Its Drivers Analyzed in Steady State for Perpetually Slower and Warmer Oceans
Authors: Pasquier Benoît , Holzer Mark , Chamberlain Matthew A. , Matear Richard J. , Bindoff Nathaniel L.
Published: September 2024

Ocean deoxygenation is an important consequence of climate change that poses an imminent threat to marine life and global food security. However, our understanding of the complex interactions between changes in circulation, solubility, and respiration that drive global‐scale deoxygenation is incomplete. Here, we consider idealized biogeochemical steady states in equilibrium with perpetually slower and warmer oceans constructed from climate‐model simulations of the 2090s that we hold constant in time. In contrast to simulations of the end‐of‐century transient state, our idealized states are intensely deoxygenated in the abyss, consistent with perpetually reduced ventilation and throttled Antarctic Bottom Water formation. We disentangle the effects of the deoxygenation drivers on preformed oxygen and true oxygen utilization (TOU) using the novel concept of upstream exposure time, which precisely connects TOU to oxygen utilization rates and preformed oxygen to ventilation. For our idealized steady states, deoxygenation below 2,000 m depth is due to increased TOU, driven dominantly by slower circulations that allow respiration to act roughly 2–3 times longer thereby overwhelming the effects of reduced respiration rates. Above 500 m depth, decreased respiration and slower circulation closely compensate, resulting in little expansion of upper‐ocean hypoxia. The bulk of preformed oxygen loss is driven by ventilation shifting equatorward to where warmer surface waters hold less oxygen. Warming‐driven declines in solubility account for less than 10% of the total oxygen loss. Although idealized, our analysis suggests that long‐term changes in the marine oxygen cycle could be driven dominantly by changes in circulation rather than by thermodynamics or biology.
The circadian clock in enamel development
Authors: Wu Ke , Li Xiaochan , Bai Yunyang , Heng Boon Chin , Zhang Xuehui , Deng Xuliang
Published: September 2024

Circadian rhythms are self-sustaining oscillations within biological systems that play key roles in a diverse multitude of physiological processes. The circadian clock mechanisms in brain and peripheral tissues can oscillate independently or be synchronized/disrupted by external stimuli. Dental enamel is a type of mineralized tissue that forms the exterior surface of the tooth crown. Incremental Retzius lines are readily observable microstructures of mature tooth enamel that indicate the regulation of amelogenesis by circadian rhythms. Teeth enamel is formed by enamel-forming cells known as ameloblasts, which are regulated and orchestrated by the circadian clock during amelogenesis. This review will first examine the key roles of the circadian clock in regulating ameloblasts and amelogenesis. Several physiological processes are involved, including gene expression, cell morphology, metabolic changes, matrix deposition, ion transportation, and mineralization. Next, the potential detrimental effects of circadian rhythm disruption on enamel formation are discussed. Circadian rhythm disruption can directly lead to Enamel Hypoplasia, which might also be a potential causative mechanism of amelogenesis imperfecta. Finally, future research trajectory in this field is extrapolated. It is hoped that this review will inspire more intensive research efforts and provide relevant cues in formulating novel therapeutic strategies for preventing tooth enamel developmental abnormalities.
Roles of microbiota in autoimmunity in Arabidopsis leaves
Authors: Cheng Yu Ti , Thireault Caitlin A. , Zhang Li , Paasch Bradley C. , Sohrabi Reza , He Sheng Yang
Published: September 2024

Over the past three decades, researchers have isolated plant mutants that show constitutively activated defence responses in the absence of pathogen infection. These mutants are called autoimmune mutants and are typically dwarf and/or bearing chlorotic/necrotic lesions. Here, from a genetic screen for Arabidopsis genes involved in maintaining a normal leaf microbiota, we identified TIP GROWTH DEFECTIVE 1 (TIP1), which encodes an S-acyltransferase, as a key player in guarding leaves against abnormal microbiota level and composition under high-humidity conditions. The tip1 mutant has several characteristic phenotypes of classical autoimmune mutants, including a dwarf stature, showing lesions, and having a high basal level of defence gene expression. Gnotobiotic experiments revealed that the autoimmune phenotypes of the tip1 mutant are largely dependent on the presence of microbiota as axenic tip1 plants have markedly reduced autoimmune phenotypes. We found that the microbiota dependency of autoimmune phenotypes is shared by several ‘lesion mimic’-type autoimmune mutants in Arabidopsis. It is worth noting that autoimmune phenotypes caused by mutations in two Nucleotide-Binding, Leucine-Rich Repeat (NLR) genes do not require the presence of microbiota and can even be partially alleviated by microbiota. Our results therefore suggest the existence of at least two classes of autoimmunity (microbiota-dependent versus microbiota-independent) in plants. The observed interplay between autoimmunity and microbiota in the lesion mimic class of autoimmunity is reminiscent of the interactions between autoimmunity and dysbiosis in the animal kingdom. These parallels highlight the intricate relationship between host immunity and microbial communities across various biological systems.
Neural correlates of bradykinesia in Parkinson’s disease: a kinematic and functional MRI study
Authors: Sarasso Elisabetta , Gardoni Andrea , Zenere Lucia , Emedoli Daniele , Balestrino Roberta , Grassi Andrea , Basaia Silvia , Tripodi Chiara , Canu Elisa , Malcangi Massimo , Pelosin Elisa , Volontè Maria Antonietta , Corbetta Davide , Filippi Massimo , Agosta Federica
Published: September 2024

Bradykinesia is defined as a “complex” of motor alterations including decreased movement amplitude and/or speed and tendency to reduce them with movement repetition (sequence effect). This study aimed at investigating the neural and kinematic correlates of bradykinesia during hand-tapping in people with Parkinson’s disease (pwPD) relative to healthy controls. Twenty-five pwPD and 25 age- and sex-matched healthy controls underwent brain functional MRI (fMRI) during a hand-tapping task: subjects alternatively opened and closed their right hand as fully and quickly as possible. Hand-tapping kinematic parameters were objectively measured during the fMRI task using an optical fibre glove. During the fMRI task, pwPD showed reduced hand-tapping amplitude (hypokinesia) and a greater sequence effect. PwPD relative to healthy controls showed a reduced activity of fronto-parietal areas, middle cingulum/supplementary motor area (SMA), parahippocampus, pallidum/thalamus and motor cerebellar areas. Moreover, pwPD showed an increased activity of brain cognitive areas such as superior temporal gyrus, posterior cingulum, and cerebellum crus I. The decreased activity of cerebellum IV–V–VI, vermis IV–V, inferior frontal gyrus, and cingulum/SMA correlated with hypokinesia and with the sequence effect. Interestingly, a reduced activity of areas involved in motor planning and timing correlated both with hypokinesia and with the sequence effect in pwPD. This study has the major strength of collecting objective motor parameters and brain activity simultaneously, providing a unique opportunity to investigate the neural correlates of the “bradykinesia complex”.
Primary succession of Bifidobacteria drives pathogen resistance in neonatal microbiota assembly
Authors: Shao Yan , Garcia-Mauriño Cristina , Clare Simon , Dawson Nicholas J. R. , Mu Andre , Adoum Anne , Harcourt Katherine , Liu Junyan , Browne Hilary P. , Stares Mark D. , Rodger Alison , Brocklehurst Peter , Field Nigel , Lawley Trevor D.
Published: September 2024

Human microbiota assembly commences at birth, seeded by both maternal and environmental microorganisms. Ecological theory postulates that primary colonizers dictate microbial community assembly outcomes, yet such microbial priority effects in the human gut remain underexplored. Here using longitudinal faecal metagenomics, we characterized neonatal microbiota assembly for a cohort of 1,288 neonates from the UK. We show that the pioneering neonatal gut microbiota can be stratified into one of three distinct community states, each dominated by a single microbial species and influenced by clinical and host factors, such as maternal age, ethnicity and parity. A community state dominated by Enterococcus faecalis displayed stochastic microbiota assembly with persistent high pathogen loads into infancy. In contrast, community states dominated by Bifidobacterium, specifically B. longum and particularly B. breve, exhibited a stable assembly trajectory and long-term pathogen colonization resistance, probably due to strain-specific functional adaptions to a breast milk-rich neonatal diet. Consistent with our human cohort observation, B. breve demonstrated priority effects and conferred pathogen colonization resistance in a germ-free mouse model. Our findings solidify the crucial role of Bifidobacteria as primary colonizers in shaping the microbiota assembly and functions in early life.
Pseudouridine guides germline small RNA transport and epigenetic inheritance
Authors: Herridge Rowan P. , Dolata Jakub , Migliori Valentina , de Santis Alves Cristiane , Borges Filipe , Schorn Andrea J. , van Ex Frédéric , Lin Ann , Bajczyk Mateusz , Parent Jean-Sebastien , Leonardi Tommaso , Hendrick Alan , Kouzarides Tony , Martienssen Robert A.
Published: September 2024

Developmental epigenetic modifications in plants and animals are mostly reset during gamete formation but some are inherited from the germline. Small RNAs guide these epigenetic modifications but how inherited small RNAs are distinguished in plants and animals is unknown. Pseudouridine (Ψ) is the most abundant RNA modification but has not been explored in small RNAs. Here, we develop assays to detect Ψ in short RNA sequences, demonstrating its presence in mouse and Arabidopsis microRNAs. Germline small RNAs, namely epigenetically activated small interfering RNAs (easiRNAs) in Arabidopsis pollen and Piwi-interacting RNAs in mouse testes, are enriched for Ψ. In pollen, pseudouridylated easiRNAs are transported to sperm cells from the vegetative nucleus, and PAUSED/HEN5 (PSD), the plant homolog of Exportin-t, interacts genetically with Ψ and is required for this transport. We further show that Exportin-t is required for the triploid block: small RNA dosage-dependent seed lethality that is epigenetically inherited from pollen. Thus, Ψ has a conserved role in marking inherited small RNAs in the germline.
A national-scale sampled temperate fuel moisture database
Authors: Ivison Katy , Little Kerryn , Orpin Alice , Lewis C. H. M. , Dyer Niamh , Keyzor Lily , Everett Luke , Stoll Erin , Andersen Roxane , Graham Laura J. , Kettridge Nicholas
Published: September 2024

Fuel moisture content (FMC) is important for the ignitability, behaviour and severity of wildfires. Understanding the drivers of FMC and its spatial and temporal variability can help us develop fuel moisture models and inform assessments of wildfire behaviour and danger. Here we present the first United Kingdom (UK) national-scale temperate FMC dataset of 8,057 samples of eighteen different fuel constituents collected across 58 sampling sites between 2021–2023. We sampled fuels across emerging fire-prone ecosystems in the UK across three studies: (1) UK-wide longer-term sampling characterising the spatio-temporal drivers of FMC; (2) landscape-scale measurement through the North Yorkshire Moors to investigate landscape-driven variability in FMC; (3) plot-scale intensive sampling in the West Midlands to quantify diurnal patterns and among-sampler variability in fuel measurements. This database addresses a global fuel moisture measurement gap within traditionally non-fire prone regions. The database will advance our understanding of temperate fuel moisture dynamics and forms a fundamental contribution towards the development of a fire danger rating system for traditionally non-fire prone regions such as the UK.
Leveraging AI and patient metadata to develop a novel risk score for skin cancer detection
Authors: Islam Shafiqul , Wishart Gordon C. , Walls Joseph , Hall Per , Seco de Herrera Alba G. , Gan John Q. , Raza Haider
Published: September 2024

Melanoma of the skin is the 17th most common cancer worldwide. Early detection of suspicious skin lesions (melanoma) can increase 5-year survival rates by 20%. The 7-point checklist (7PCL) has been extensively used to suggest urgent referrals for patients with a possible melanoma. However, the 7PCL method only considers seven meta-features to calculate a risk score and is only relevant for patients with suspected melanoma. There are limited studies on the extensive use of patient metadata for the detection of all skin cancer subtypes. This study investigates artificial intelligence (AI) models that utilise patient metadata consisting of 23 attributes for suspicious skin lesion detection. We have identified a new set of most important risk factors, namely “C4C risk factors”, which is not just for melanoma, but for all types of skin cancer. The performance of the C4C risk factors for suspicious skin lesion detection is compared to that of the 7PCL and the Williams risk factors that predict the lifetime risk of melanoma. Our proposed AI framework ensembles five machine learning models and identifies seven new skin cancer risk factors: lesion pink, lesion size, lesion colour, lesion inflamed, lesion shape, lesion age, and natural hair colour, which achieved a sensitivity of $$80.46\pm 2.50\%$$

80.46
±
2.50
%

and a specificity of $$62.09\pm 1.90\%$$

62.09
±
1.90
%

in detecting suspicious skin lesions when evaluated using the metadata of 53,601 skin lesions collected from different skin cancer diagnostic clinics across the UK, significantly outperforming the 7PCL-based method (sensitivity $$68.09\pm 2.10\%$$

68.09
±
2.10
%

, specificity $$61.07\pm 0.90\%$$

61.07
±
0.90
%

) and the Williams risk factors (sensitivity $$66.32\pm 1.90\%$$

66.32
±
1.90
%

, specificity $$61.71\pm 0.6\%$$

61.71
±
0.6
%

). Furthermore, through weighting the seven new risk factors we came up with a new risk score, namely “C4C risk score”, which alone achieved a sensitivity of $$76.09\pm 1.20\%$$

76.09
±
1.20
%

and a specificity of $$61.71\pm 0.50\%$$

61.71
±
0.50
%

, significantly outperforming the 7PCL-based risk score (sensitivity $$73.91\pm 1.10\%$$

73.91
±
1.10
%

, specificity $$49.49\pm 0.50\%$$

49.49
±
0.50
%

) and the Williams risk score (sensitivity $$60.68\pm 1.30\%$$

60.68
±
1.30
%

, specificity $$60.87\pm 0.80\%$$

60.87
±
0.80
%

). Finally, fusing the C4C risk factors with the 7PCL and Williams risk factors achieved the best performance, with a sensitivity of $$85.24\pm 2.20\%$$

85.24
±
2.20
%

and a specificity of $$61.12\pm 0.90\%$$

61.12
±
0.90
%

. We believe that fusing these newly found risk factors and new risk score with image data will further boost the AI model performance for suspicious skin lesion detection. Hence, the new set of skin cancer risk factors has the potential to be used to modify current skin cancer referral guidelines for all skin cancer subtypes, including melanoma.
Effectiveness of whole-body electromyostimulation on knee pain and physical function in knee osteoarthritis: a randomized controlled trial
Authors: Kast Stephanie , Kemmler Wolfgang , Roemer Frank W. , Kohl Matthias , Culvenor Adam G. , Mobasheri Ali , Uder Michael , von Stengel Simon
Published: September 2024

In a randomized, controlled study, whole-body electromyostimulation (WB-EMS) was investigated as a promising alternative treatment technique compared to conventional strength training for the management of knee osteoarthritis (OA). Seventy-two overweight participants with symptomatic knee OA were randomly assigned to WB-EMS (n = 36) or a usual care group (UCG, n = 36). For seven months, the WB-EMS group received three times per fortnight a WB-EMS training, while the UCG was prescribed six-times physiotherapeutic treatments. We observed significant effects for the primary outcome “pain”, as determined by the Knee injury and Osteoarthritis Outcome Score (KOOS), with more favourable changes in the WB-EMS group vs UCG (between-group difference 9.0 points, 95%CI 2.9–15.1, p = 0.004). Secondary outcomes, including the other KOOS subscales (symptoms, function in daily living, function in sports/recreational activities and quality of life), 7 day pain diary, hip/leg extensor strength and lower limb function (30s sit-to-stand test), were also statistically significant in favour of the WB-EMS group. Overall, WB-EMS was found to be effective in relieving knee pain symptoms and improving physical function in individuals with symptomatic knee OA compared to usual care treatment. WB-EMS could be used as an alternative therapy in the management of knee OA; particularly for patients that cannot be motivated for conventional training.
High performance ultra-thin lithium metal anode enabled by vacuum thermal evaporation
Authors: Rospars Nicolas , Srout Mohammed , Fu Chengyin , Mourouga Gaël , Mensi Mounir , Ingenito Andrea
Published: September 2024

The passivation layer that naturally forms on the lithium metal surface contributes to dendrite formation in lithium metal batteries by affecting lithium nucleation uniformity during charging. Herein, we propose using vacuum thermal evaporation to produce a high-performance ultra-thin lithium metal anode (≤25 µm) with a native layer much thinner than that of extruded lithium. The evaporated lithium metal shows significantly reduced charge-transfer resistance, resulting in uniform and dense lithium plating in both carbonate and ether electrolytes. This study reveals that the evaporated lithium metal outperforms the extruded version in ether electrolyte and with LiFePO4 cathodes, showing a 30% increase in cycle life. Additionally, when paired with LiNi0.6Mn0.2Co0.2O2 cathodes in carbonate electrolyte, the evaporated anode’s cycle life is tripled compared to the extruded lithium metal. This demonstrates that vacuum thermal evaporation is a viable method for producing ultra-thin lithium metal anodes that prevent dendrite growth due to their excellent surface condition.
Forging out-of-equilibrium supramolecular gels
Authors: Bianco Simona , Hallam Stewart Fin , Panja Santanu , Zyar Asra , Bowley Emma , Bek Marko , Kádár Roland , Terry Ann , Appio Roberto , Plivelic Tomás S. , Maguire Mahon , Poptani Harish , Marcello Marco , Sonani Ravi R. , Egelman Edward H. , Adams Dave J.
Published: September 2024

The design of supramolecular hydrogels comprising aligned domains is important for the fabrication of biomimetic materials and applications in optoelectronics. One way to access such materials is by the self-assembly of small molecules into long fibres, which can be aligned using an external stimulus. Out-of-equilibrium supramolecular gels can also be designed, where pre-programmed changes of state can be induced by the addition of chemical fuels. Here we exploit these dynamic properties to form materials with aligned domains through a ‘forging’ approach: an external force is used to rearrange the underlying network from random to aligned fibres as the system undergoes a pre-programmed gel-to-sol-to-gel transition. We show that we can predictably organize the supramolecular fibres, leading to controllable formation of materials with aligned domains through a high degree of temporal control.