bluuebunny/crossref_metadata_2025 huggingface dataset:
First Clinical Experiences Using Preconditioning Approaches to Improve MSC-Based Therapies
Authors: Le Bryan , Cressman Amin , Morales David , Fierro Fernando A.
Published: January 2024

Purpose of Review

Describe the rationale for preconditioning MSCs prior to use as therapy and the state-of-the-art of using preconditioning of MSCs in clinical settings.

Recent Findings

Mounting preclinical data supports preconditioning of mesenchymal stromal cells (MSCs) to enhance their therapeutic efficacy. Most research has focused on cytokine priming and hypoxic preconditioning, while other approaches, such as glycoengineering, remain relatively understudied. Despite strong preclinical data, clinical evidence supporting preconditioning strategies are limited to six Phase I clinical trials (most of them in progress).

Here, we succinctly discuss the rationale for preconditioning using cytokines, hypoxia, and glycoengineering, while elaborating on the respective clinical experiences. Overall, we note that preconditioning is highly dependent on the desired application, and therefore requires elucidating the mechanism of action of the MSCs used for therapy. Preconditioning may also help mitigate heterogeneity of MSC lots. Based on the remarkable safety profile of MSCs, even when used in allogeneic settings, the role of preconditioning prior to their final formulation might be the key to reach expected therapeutic outcomes.
Influence of Cooling Rate and Alloying by “Cr, V, and Ni” on Microstructure and High-Temperature Wear Behavior of SiMo Ductile Iron
Authors: Abdelrahim Dawlat M. , Ateia Ebtesam E. , Youssef Mervat , Nofal Adel A.
Published: January 2024

SiMo ductile irons, typical heat-resistant materials, are subjected to varied wear environments during operation in high-temperature applications. SiMo ductile iron castings of different thicknesses were cast in investment and greensand molds, achieving a wide range of cooling rates. The present work aims to investigate the effect of the cooling rate and alloying elements (Cr, V, and Ni) on the microstructure and the abrasive wear behavior of these grades of SiMo ductile iron at high-temperature 700 °C under different loads. Thermodynamic calculations were used to propose the phase diagrams, critical transformation temperatures, and phase volume fractions in all SiMo alloys by using the Thermo-Calc software then verified by and Differential Scanning Calorimetry (DSC). The microstructure of unalloyed SiMo ductile cast iron consists of graphite nodules and carbides embedded in the precipitates at the grain boundary regions in a ferrite matrix. The alloyed SiMo microstructure contains nodular graphite and the carbides promoted by the alloying elements (Cr and V). The alloyed SiMo alloys exhibit higher wear resistance than unalloyed ones. These wear results support that the microstructure plays a chief role in wear loss. The combination of M6C, VC, and M7C3 carbides embedded in a ferrite-pearlite matrix (alloyed SiMo) seems to be more resistant to wear than the ferritic matrix with lamellar pearlite and eutectic M6C carbides (unalloyed SiMo).
Cultural expertise in Sami land rights litigation: Epistemic strategies in the Girjas and Fosen cases
Authors: Johansson Peter , Schaffer Johan Karlsson , Johansson Lopez Sara , Palm Sofie , Parguel Camille , Sandin Ina
Published: January 2024

How do parties mobilise cultural expertise in Indigenous rights litigation in Scandinavia? Recently, Sami groups have litigated to claim Indigenous rights to land and natural resources, winning some remarkable victories in the Supreme Courts of Norway and Sweden. In this paper, we draw on socio-legal mobilisation theory to analyse the epistemic strategies of Sami litigants and their adversaries in two recent landmark Supreme Court cases on Indigenous rights to usage of land: the 2020 Girjas case in Sweden and the 2021 Fosen case in Norway. Conceptualising cultural expertise as a strategic framing contest, we analyse how the parties struggled over the epistemic basis of the respective case by legitimating their claims to cultural knowledge, drawing on academic research, and discrediting their opponents’ epistemic claims. Our findings suggest that in both cases, Sami claimants successfully established an epistemic basis where their traditional, experiential knowledge combined with independent academic expertise effectively challenged the knowledge claims of their adversaries. Yet, both cases also demonstrate how the linkage between Sami Indigeneity and reindeer husbandry in the national law of both countries excludes non-reindeer herding Sami persons from the Indigenous rights affirmed by the courts.
Powdery mildew of ash trees caused by the non-native Erysiphe salmonii in Hungary
Authors: Pintye Alexandra , Molnár Orsolya , Soós Anita Z. , Seress Diána , Ágoston János , Németh Márk Z.
Published: January 2024

Fraxinus ornus and F. excelsior are naturally occurring woodland trees and widely cultivated ornamental plants in Hungary. Leaves with powdery mildew symptoms observed unusually on adaxial side of leaves of F. ornus and F. excelsior were collected from two locations in Hungary. We identified the causing fungi based on their morphological characteristics and molecular phylogenetic analysis. Numerous chasmothecia were found on a part of the samples, which were spherical, 83–120 µm in diameter, and the apices of the appendages uncinated or spirally curved. Anamorphs were characterized by conidiophores developing conidia singly, and by hyphae with lobed appressoria, characteristic of Erysiphe spp. The internal transcribed spacer region of the nrDNA was amplified, and the BLAST searches showed 100% similarity with Erysiphe salmonii sequences in GenBank. In the phylogenetic analysis the sequences of the Hungarian samples grouped in one clade with the sequences of other E. salmonii specimens collected in Central and Eastern Europe and Asia. This is the first report of the non-native E. salmonii causing powdery mildew on Fraxinus sp. in Hungary.
Actively Learning to Learn Causal Relationships
Authors: Jiang Chentian , Lucas Christopher G.
Published: January 2024

How do people actively learn to learn? That is, how and when do people choose actions that facilitate long-term learning and choosing future actions that are more informative? We explore these questions in the domain of active causal learning. We propose a hierarchical Bayesian model that goes beyond past models by predicting that people pursue information not only about the causal relationship at hand but also about causal overhypotheses—abstract beliefs about causal relationships that span multiple situations and constrain how we learn the specifics in each situation. In two active “blicket detector” experiments with 14 between-subjects manipulations, our model was supported by both qualitative patterns in participant behavior and an individual differences-based model comparison. Our results suggest when there are abstract similarities across active causal learning problems, people readily learn and transfer overhypotheses reflecting these similarities. Moreover, people exploit these overhypotheses to facilitate long-term active learning.
How a Daily Regimen of Operant Conditioning Might Explain the Power of the Search Engine Manipulation Effect (SEME)
Authors: Epstein Robert , Lothringer Michael , Zankich Vanessa R.
Published: January 2024

Recent studies have shown that biased search results can produce substantial shifts in the opinions and voting preferences of undecided voters – a phenomenon called the “search engine manipulation effect” (SEME), one of the most powerful list effects ever discovered. We believe this is so because, unlike other list effects, SEME is supported by a daily regimen of operant conditioning. When people conduct searches for simple facts (86% of searches), the correct answer invariably turns up in the top position, which teaches users to attend to and click on high-ranking search results. As a result, when people are undecided, they tend to formulate opinions based on web pages linked to top search results. We tested this hypothesis in a controlled experiment with 551 US voters. Participants in our High-Trust group conducted routine searches in which the correct answer always appeared in the first search result. In our Low-Trust group, the correct answer could appear in any search position other than the first two. In all, participants had to answer five questions during this pre-training, and we focused our analysis on people who answered all the questions correctly (n = 355) – in other words, on people who were maximally impacted by the pre-training contingencies. A difference consistent with our hypothesis emerged between the groups when they were subsequently asked to search for information on political candidates. Voting preferences in the High-Trust group shifted toward the favored candidate at a higher rate (34.6%) than voting preferences in the Low-Trust group (17.1%, p = 0.001).
Resveratrol Improves Mechanical Allodynia and Inflammation: Focus on Sex Differences in Rats
Authors: Bautista-Carro Mario Alberto , Galindo-Paredes Gumaro , Iannitti Tommaso , Morales-Medina Julio César
Published: January 2024

Inflammatory pain is a complex phenomenon arising from various etiological factors, resulting in diverse symptoms that can lead to persistent debilitations. The management of chronic inflammatory pain predominantly involves non-steroidal anti-inflammatory drugs, despite their association with adverse cardiovascular and gastrointestinal effects. Consequently, the pursuit of innovative therapeutic avenues for pain intervention is of paramount importance. Resveratrol, renowned for its anti-inflammatory and anti-oxidative attributes, emerges as a promising candidate in this regard. In this work, we assessed the potential of resveratrol to elicit anti-nociceptive and anti-inflammatory effects in two distinct models of peripheral inflammation: carrageenan and complete Freund’s adjuvant, conducted in male and female rats. In rats treated with carrageen, resveratrol administration yielded an elevation in mechanical thresholds in both sexes, concurrently inducing a reduction in paw diameter specifically among male rats. Furthermore, the administration of resveratrol in complete Freund’s adjuvant–treated rats led to an analogous increase of mechanical thresholds, a response observed in both male and female subjects. These compelling outcomes underscore the analgesic and anti-inflammatory attributes inherent to resveratrol, thereby offering a fresh insight into the intricate realm of sex-related variances in two well-characterized pharmacodynamics models of inflammatory pain.

Graphical Abstract
A Nomogram Model to Predict Deep Vein Thrombosis Risk After Surgery in Patients with Hip Fractures
Authors: Bo Ruting , Chen Xiaoyu , Zheng Xiuwei , Yang Yang , Dai Bing , Yuan Yu
Published: January 2024

Aims

This study aimed to establish a nomogram model for predicting the probability of postoperative deep vein thrombosis (DVT) risk in patients with hip fractures.

Methods

504 patients were randomly assigned to the training set and validation set, and then divided into a DVT group and a non-DVT group. The study analysed the risk factors for DVT using univariate and multivariate analyses. Based on these parameters, a nomogram model was constructed and validated. The predicting performance of nomogram was evaluated by discrimination, calibration, and clinical usefulness.

Results

The predictors contained in the nomogram model included age, surgical approach, 1-day postoperative D-dimer value and admission ultrasound diagnosis of the lower limb vein. Furthermore, the area under the ROC curve (AUC) for the specific DVT risk-stratification nomogram model (0.815; 95% CI 0.746–0.884) was significantly higher than the current model (Caprini) (0.659; 95% CI 0.572–0.746, P < 0.05). According to the calibration plots, the prediction and actual observation were in good agreement. In the range of threshold probabilities of 0.2–0.8, the predictive performance of the model on DVT risk could be maximized.

Conclusions

The current predictive model could serve as a reliable tool to quantify the possibility of postoperative DVT in hip fractures patients.
Concerning the ignition of a C12A7 electride plasma-based cathode
Authors: Drobny Christian , Tajmar Martin
Published: January 2024

Hollow cathodes are crucial components for many electric propulsion systems used for space applications. However, they also represent a challenging and sometimes even limiting element for the propulsion systems. Particularly in recent times when alternative propellants are under evaluation for the thruster, and the design and the limits of the cathodes are being pushed. Consequently, significant improvement in the technology is desired. This publication tests a heaterless cathode using the emitter material C12A7 electride, particularly reviewing its ignition behavior and performance during an ignition cycling campaign. Stable heaterless ignition has been reliantly achieved in only a few milliseconds at an ignition potential of less than 400 V and 20 sccm Kr flow rate. Furthermore, two ignition cycling campaigns at different flow rates are presented, one reaching 3300 ignitions, the other igniting at only 6 sccm Kr flow rate. The degradation of the emitter materials and the influence on the ignition performance is discussed.
Can Construction Grammar Be Proven Wrong?
Authors: Cappelle Bert
Published: January 2024

Construction Grammar has gained prominence in linguistics, owing its popularity to its inclusive approach that considers language units of varying sizes and generality as potential constructions – mentally stored form-function units. This Element serves as a cautionary note against complacency and dogmatism. It emphasizes the enduring importance of falsifiability as a criterion for scientific hypotheses and theories. Can every postulated construction, in principle, be empirically demonstrated not to exist? As a case study, the author examines the schematic English transitive verb-particle construction, which defies experimental verification. He argues that we can still reject its non-existence using sound linguistic reasoning. But beyond individual constructions, what could be a crucial test for Construction Grammar itself, one that would falsify it as a theory? In making a proposal for such a test, designed to prove that speakers also exhibit pure-form knowledge, this Element contributes to ongoing discussions about Construction Grammar's theoretical foundations.
Intersectional Advocacy
Authors: Perez Brower Margaret
Published: January 2024

What happens to those living at the margins of US politics and policy – trapped between multiple struggles: gender-based violence, poverty, homelessness, unaffordable healthcare, mass incarceration and immigration? In this book, Margaret Perez Brower offers the concept of 'intersectional advocacy' to reveal how select organizations addressing gender-based violence are closing policy gaps that perpetuate inequalities by gender, race, ethnicity, and class. Intersectional advocacy is a roadmap for rethinking public policy. The book captures how advocacy groups strategically contest, reimagine, and reconfigure policy institutions using comprehensive new strategies that connect issues together. As these groups challenge traditional ways of addressing the most pressing social issues in the US, they uncover deep inequities that are housed within these institutions. Ultimately, organizations practicing intersectional advocacy illuminate how to redraw the boundaries of policies in ways that transform US democracy to be more representative, equitable, and just.
Global China's Shadow Exchange
Authors: Ngo Tak-Wing
Published: January 2024

This Element shows China has assumed a historical role in shaping a new turn in globalization. It has assertively engaged in the open globalizing process through its Belt and Road Initiative as well as in the clandestine process through its shadow networks. These networks have incorporated millions of common people who are unwitting agents of transnational exchange in a global shadow economy. In contrast to the neoliberal phase, the shadow turn in globalization is driven by a plurality of individual, corporate, and state actors with unique divisions of labour, hierarchies of control and domination, and modes of operation. By virtue of being a nodal centre for shadow operations, China is exerting its shadow power in regrouping global city networks, redefining global value chains, and reconfigurating state borders and power.
Ophthalmic and Neuroimaging Associations In Optic Nerve Hypoplasia/Septo-Optic-Pituitary Dysplasia
Authors: Salman Michael S. , Hossain Shakhawat , Carson Elizabeth , Clark Ian H. , Rozovsky Katya
Published: January 2024

Background:

Optic nerve hypoplasia (ONH) and septo-optic-pituitary dysplasia (SOD) are neurodevelopmental disorders associated with congenital visual impairment. Our aim was to investigate associations between several ophthalmic and neuroimaging features in patients with ONH/SOD.

Methods:

A retrospective chart and neuroimaging review was performed in patients with ONH/SOD. Ophthalmic signs (e.g., monocular best-corrected visual acuity [BCVA], nystagmus, and strabismus) and neuroimaging data were extracted and their associations were investigated.

Results:

There were 128 patients (70 males) with ONH/SOD who had neuroimaging. Their mean age at the end of the study was 13.2 (SD: 7.5) years. Ophthalmic data were available on 102 patients (58 males). BCVA varied from normal to no light perception. There were statistically significant associations between: (A) Reduced optic nerve or chiasm size on neuroimaging and more severely impaired BCVA and (B) laterality of the reduced optic nerve or chiasm size on neuroimaging and laterality of: (1) The eye with reduced BCVA, (2) small optic disc size, and (3) RAPD, if present (p ≤ 0.0002 each). The presence of symmetrically small optic nerves on MRI was significantly more common in patients with nystagmus than when nystagmus was absent (N = 96, 75% vs. 38.6%, p < 0.0001). The presence of neuronal migration disorders, their type and laterality were not associated with BCVA and laterality of the reduced BCVA.

Conclusion:

The functional and structural associations in ONH are consistent with the impaired visual function that results from the hypoplastic anterior visual pathways. However, these associations were not perfectly concordant making prediction of adult BCVA challenging in these patients.
Chern classes in equivariant bordism
Authors: Schwede Stefan
Published: January 2024

We introduce Chern classes in

$U(m)$

-equivariant homotopical bordism that refine the Conner–Floyd–Chern classes in the

$\mathbf {MU}$

-cohomology of

$B U(m)$

. For products of unitary groups, our Chern classes form regular sequences that generate the augmentation ideal of the equivariant bordism rings. Consequently, the Greenlees–May local homology spectral sequence collapses for products of unitary groups. We use the Chern classes to reprove the

$\mathbf {MU}$

-completion theorem of Greenlees–May and La Vecchia.
Controls of lithology and climate over chemical weathering trends: new insights from the precipitation-dominated Dokriani glacier, central Himalaya, India
Authors: Sundriyal Shipika , Shukla Tanuj , Kang Shichang , Zhang Yulan , Dobhal Dwarika Prasad , Singh Rajesh
Published: January 2024

The chemical composition of meltwater-draining Himalayan glacierized basins reflects the dominance of carbonic acid in weathering of silicate and carbonate minerals, yet the role of sulfuric acid-mediated reactions in the mineral weathering and ionic release is still unclear. Here, we present a long-term study (1992–2018) of chemical weathering characteristics of a precipitation-dominated glacierized basin (Dokriani glacier) of central Himalaya. By using new and reprocessed datasets of major ions from the glacial/subglacial zones of the glacier, we suggest that two-thirds of the dissolved load of the meltwater derives from sulfuric acid-mediated weathering of minerals and rocks. We observed a clear control of carbonic acid-mediated reactions in the early ablation periods, while sulfuric acid-mediated reactions dominate in peak and late ablation periods. The slopes and intercepts in best-fit regressions of [*Ca2+ + *Mg2+ vs *SO42− and HCO3−] and [HCO3− vs *SO42−] in meltwater were following the stoichiometric parameters of sulfide oxidation coupled to carbonate dissolution reactions. The glaciers of the central and western Himalaya are in good agreement with the present estimates. We contend that the bedrock lithology has limited or second-order effects over the ionic release from Himalayan glaciers and surmise that these patterns are broadly applicable to the other orogenic systems of the world.
Sharp large deviations and concentration inequalities for the number of descents in a random permutation
Authors: Bercu Bernard , Bonnefont Michel , Richou Adrien
Published: January 2024

The goal of this paper is to go further in the analysis of the behavior of the number of descents in a random permutation. Via two different approaches relying on a suitable martingale decomposition or on the Irwin–Hall distribution, we prove that the number of descents satisfies a sharp large-deviation principle. A very precise concentration inequality involving the rate function in the large-deviation principle is also provided.
Association between sleep duration and quality with food intake, chrononutrition patterns, and weight gain during pregnancy
Authors: Silveira Noara Carvalho , Balieiro Laura Cristina Tibiletti , Gontijo Cristiana Araújo , Teixeira Gabriela Pereira , Fahmy Walid Makin , Maia Yara Cristina de Paiva , Crispim Cibele Aparecida
Published: January 2024

To analyse the association between sleep duration and quality with food intake, chrononutrition patterns, and weight gain during pregnancy. A prospective cohort study was conducted with 100 pregnant women. Data collection occurred once during each gestational trimester. The assessment of sleep quality and duration was performed using the Pittsburgh Sleep Quality Index. Food intake was assessed using three 24-h recalls in each trimester. Body weight was measured during the three trimesters, and height was measured only once to calculate the BMI. Linear regression analyses were performed to associate sleep duration and quality with food consumption and weight gain variables. Longer sleep duration was associated with a later dinner in the first trimester (β = 0·228, P = 0·025) and earlier in the third trimester (β = –0·223, P = 0·026), in addition to a later morning snack in the second trimester (β = 0·315, P = 0·026). Worse sleep quality was associated with higher total energy intake (β = 0·243, P = 0·044), total fat (β = 0·291, P = 0·015) and the chrononutrition variables such as a higher number of meals (β = 0·252, P = 0·037), higher energetic midpoint (β = 0·243, P = 0·044) and shorter fasting time (β = –0·255, P = 0·034) in the third trimester. Sleep quality was also associated with a higher BMI in the first trimester of pregnancy (β = 0·420, P = < 0·001). Most of the associations found in the present study show that poor sleep is associated with higher energy and fat intake and higher BMI. Longer sleep duration was associated with a later dinner in early pregnancy and an earlier dinner in late pregnancy, as well as with a later morning snack in the second trimester of pregnancy.
Caregivers’ concerns through health professionals’ eyes
Authors: Oliveira Carolina , Lourenço Daniela , Sotero Luciana , Relvas Ana Paula
Published: January 2024

Objectives

Advancements in medicine and science have enabled more and more people to live longer with a chronic medical condition, namely cancer. Nevertheless, the palliative care (PC) approach continues to be introduced and incorporated later in the lives of patients and families dealing with such conditions. Thus, the need for individuals to care for this population in our society is increasing, giving rise to the so-called “informal caregivers.” The present study intends to examine the main obstacles faced by informal caregivers taking care of a cancer patient receiving PC based on what health professionals working in these settings perceive and write down. To achieve this goal, the written files of 2 Portuguese palliative care institutions were analyzed.

Methods

An inductive thematic analysis was conducted, focusing on the contact between health professionals and family caregivers and based on the notes taken by health professionals.

Results

Three main overarching themes were identified: (1) burden, (2) intra-family impact of the illness, and (3) network vulnerabilities. Included in this are the emphasis on the role of the family and social support, the high levels of psychological morbidity and caregiver burden present over this period, and a great need for information about the illness.

Significance of results

This study provided a broader awareness regarding the daily struggle experienced by family caregivers, particularly those who juggle between “roles.” It is vital to understand the scope of the obstacles experienced by caregivers during the terminal phase of their loved one’s illness, given how important it is to address the family’s needs. Future studies and practitioners should consider these observations and topics when considering new approaches for this population, as they ought to be quite focused and short in time in order to meet people’s needs.
Nonparametric intercept regularization for insurance claim frequency regression models
Authors: Lee Gee Y. , Jeong Himchan
Published: January 2024

In a subgroup analysis for an actuarial problem, the goal is for the investigator to classify the policyholders into unique groups, where the claims experience within each group are made as homogenous as possible. In this paper, we illustrate how the alternating direction method of multipliers (ADMM) approach for subgroup analysis can be modified so that it can be more easily incorporated into an insurance claims analysis. We present an approach to penalize adjacent coefficients only and show how the algorithm can be implemented for fast estimation of the parameters. We present three different cases of the model, depending on the level of dependence among the different coverage groups within the data. In addition, we provide an interpretation of the credibility problem using both random effects and fixed effects, where the fixed effects approach corresponds to the ADMM approach to subgroup analysis, while the random effects approach represents the classic Bayesian approach. In an empirical study, we demonstrate how these approaches can be applied to real data using the Wisconsin Local Government Property Insurance Fund data. Our results show that the presented approach to subgroup analysis could provide a classification of the policyholders that improves the prediction accuracy of the claim frequencies in case other classifying variables are unavailable in the data.
Observational Learning in Ab Initio Pilot Training
Authors: Marques Elvira , Carim Jr Guido , Campbell Chris , Lohmann Gui
Published: January 2024

Abstract: New learning and teaching techniques are required to reduce the length and costs of flight training while increasing its quality, such as observational learning, also known as backseating in aviation training. This study investigates the opportunities and challenges associated with backseating in an aircraft when another student is learning to fly. An ethnographic study of a flight school in Australia was conducted via observation and in-depth interviews. The results show opportunities such as learning from common mistakes, recognizing patterns, and reinforcing struggling areas in a stress-free environment, without any extra costs. The reported concerns included weight limits and regulatory issues, student nervousness when observed, and insufficient time to backseat flights. For backseating to be adopted, regulatory ambiguities should be addressed.
Emission Factors From Wildfires in the Western US: An Investigation of Burning State, Ground Versus Air, and Diurnal Dependencies During the FIREX‐AQ 2019 Campaign
Authors: Fiddler Marc N. , Thompson Chelia , Pokhrel Rudra P. , Majluf Francesca , Canagaratna Manjula , Fortner Edward C. , Daube Conner , Roscioli Joseph R. , Yacovitch Tara I. , Herndon Scott C. , Bililign Solomon
Published: January 2024

Emission factors (EFs) are crucial in understanding the effects of wildfire emissions on air quality. We examined the variability of EFs of three wildfires (Nethker, Castle, and 204 Cow) during the 2019 Western US wildfire season using the Aerodyne Mobile Laboratory (AML) and compared them to previous studies. The AML sampling captured the high degree of variability present in wildfires, and we report results for a range of combustion conditions that is more extensive than previous field and laboratory studies. For instance, we captured emissions from freshly started flaming fuels and we report rare EF measurements at very high modified combustion efficiencies (MCEs); MCEs >0.9. Differences in emissions between AML‐observed wildfires were attributed to burning state/MCE rather than fuel type. A comparison of EFs versus MCE was made and linear fits were compared to previous observations to reveal important differences that incorporate these high MCEs. For some species, there remains an EF dependence on MCE at these high values, while others reach a minimum value and exhibit either no or a weak dependence above it. EF differences were found for many of the studied compounds when comparing ground‐based and airborne observations, with generally greater airborne EFs possibly due to photochemical oxidation. The largest differences were from monoterpenes and acetaldehyde. Comparisons were made between AML‐observed wildfires, aircraft observations, and the values in literature for EFs and emission ratios, with mixed agreement due to the high degree of variability caused by differences in MCE. Differences in MCE drove the diurnal EF differences.
Tropical Cirrus Are Highly Sensitive to Ice Microphysics Within a Nudged Global Storm‐Resolving Model
Authors: Atlas R. L. , Bretherton C. S. , Sokol A. B. , Blossey P. N. , Khairoutdinov M. F.
Published: January 2024

Cirrus dominate the longwave radiative budget of the tropics. For the first time, the variability in cirrus properties and longwave cloud radiative effects (CREs) that arises from using different microphysical schemes within nudged global storm‐resolving simulations from a single model, is quantified. Nudging allows us to compute radiative biases precisely using coincident satellite measurements and to fix the large‐scale dynamics across our set of simulations to isolate the influence of microphysics. We run 5‐day simulations with four commonly‐used microphysics schemes of varying complexity (SAM1MOM, Thompson, M2005 and P3) and find that the tropical average longwave CRE varies over 20 W m−2 between schemes. P3 best reproduces observed longwave CRE. M2005 and P3 simulate cirrus with realistic frozen water path but unrealistically high ice crystal number concentrations which commonly hit limiters and lack the variability and dependence on frozen water content seen in aircraft observations. Thompson and SAM1MOM have too little cirrus.
Process‐Informed Subsampling Improves Subseasonal Rainfall Forecasts in Central America
Authors: Kowal Katherine M. , Slater Louise J. , Li Sihan , Kelder Timo , Hall Kyle J. C. , Moulds Simon , García‐López Alan A. , Birkel Christian
Published: January 2024

Subseasonal rainfall forecast skill is critical to support preparedness for hydrometeorological extremes. We assess how a process‐informed evaluation, which subsamples forecasting model members based on their ability to represent potential predictors of rainfall, can improve monthly rainfall forecasts within Central America in the following month, using Costa Rica and Guatemala as test cases. We generate a constrained ensemble mean by subsampling 130 members from five dynamic forecasting models in the C3S multimodel ensemble based on their representation of both (a) zonal wind direction and (b) Pacific and Atlantic sea surface temperatures (SSTs), at the time of initialization. Our results show in multiple months and locations increased mean squared error skill by 0.4 and improved detection rates of rainfall extremes. This method is transferrable to other regions driven by slowly‐changing processes. Process‐informed subsampling is successful because it identifies members that fail to represent the entire rainfall distribution when wind/SST error increases.
Relationships Between Land Use and Terrestrial Organic Matter Transfer to the Baltic Sea Over the Last 500 Years
Authors: Yang Bingjie , Ljung Karl , Ning Wenxin , Filipsson Helena L. , Nielsen Anne Birgitte
Published: January 2024

Terrestrial organic matter (OM) plays a key role in coastal organic carbon burial. However, few studies focus on the relationship between land use in the watershed and the transport of terrestrial OM to coasts from a long‐term perspective. In this study, we compared terrestrial OM deposition between an inlet of the Baltic Sea and an upstream lake within the same watershed over the last 500 years, using lignin biomarkers in the sediments. In combination with pollen‐based quantitative land cover reconstruction, we assessed the impacts of semicentennial‐scale changes in land use on terrestrial OM export. The results indicated that the concentration, composition, and degradation state of the lignin‐derived OM differed substantially between the two sites. The lake received larger amounts of lignin‐derived OM during periods of intensified agriculture, but the coastal site did not. The composition of lignin in the coastal sediment did not directly reflect variations in vegetation cover in the watershed. The reason could be that the OM was settled in the upstream basins. Furthermore, the terrestrial OM that did reach the coastal sediments was modified through degradation during the transport, and only the refractory component was deposited at the coast in a relatively unaltered form.
Extending Active Network Length Versus Catchment Discharge Relations to Temporarily Dry Outlets
Authors: Botter Gianluca , McNamara James , Durighetto Nicola
Published: January 2024

River networks are not steady blue lines drawn in a map, since they continuously change their shape and extent in response to climatic drivers. Therefore, the flowing length of rivers (L) and the corresponding catchment‐scale streamflow (Qsur) co‐evolve dynamically. This paper analyzes the relationship between the wet channel length and the streamflow of a river basin, formulating a general analytical model that includes the case of temporarily dry outlets. In particular, the framework relaxes the common assumption that when the discharge at the outlet tends to zero the upstream flowing length approaches zero. Different analytical expressions for the L(Qsur) law are derived for the cases of (a) a perennial outlet; (b) a non‐perennial outlet that dries out only when the whole network is dry; and (c) a temporarily dry outlet, that experiences surface flow for less time than other network nodes. In all cases, the shape of the L(Qsur) relationship is controlled by the distribution of the specific subsurface discharge capacity along the network. For temporarily dry outlets, however, the relation between L and Qsur might depend on an unknown shifting factor. Three real‐world examples are presented to demonstrate the flexibility and the robustness of the theory. Our results indicate that the whole shape of the L(Qsur) relation might not be empirically observable if a significant fraction of the network is perennial or some reaches in the network experience surface flow for longer than the discharge gauging station. The study provides a basis for integrating empirical L(Qsur) data gathered in diverse sites.
Mapping the Moon to Shield Astronauts from Radiation
Authors: Bouch�r Sierra
Published: January 2024

Scientists are charting landing spots that offer future lunar astronauts protection from the Sun and deep space.
Soluble receptors in cancer: mechanisms, clinical significance, and therapeutic strategies
Authors: Park Eun-Ji , Lee Chang-Woo
Published: January 2024

Soluble receptors are soluble forms of receptors found in the extracellular space. They have emerged as pivotal regulators of cellular signaling and disease pathogenesis. This review emphasizes their significance in cancer as diagnostic/prognostic markers and potential therapeutic targets. We provide an overview of the mechanisms by which soluble receptors are generated along with their functions. By exploring their involvement in cancer progression, metastasis, and immune evasion, we highlight the importance of soluble receptors, particularly soluble cytokine receptors and immune checkpoints, in the tumor microenvironment. Although current research has illustrated the emerging clinical relevance of soluble receptors, their therapeutic applications remain underexplored. As the landscape of cancer treatment evolves, understanding and targeting soluble receptors might pave the way for novel strategies for cancer diagnosis, prognosis, and therapy.
Twisted microdomains in liquid crystals for polarization-insensitive phase modulation
Authors: Ma Yifei , Zhao Zimo , Morris Stephen M. , He Chao
Published: January 2024

Polarization-independent phase modulators based upon liquid crystals (LCs) with a simple device architecture have long been desired for a range of optical applications. Recently, researchers have demonstrated a novel fabrication procedure using cholesteric LCs as a primer for achieving low polarization dependence coupled with a large phase modulation depth.
Cavity-enhanced photoacoustic dual-comb spectroscopy
Authors: Wang Zhen , Nie Qinxue , Sun Haojia , Wang Qiang , Borri Simone , De Natale Paolo , Ren Wei
Published: January 2024

Photoacoustic dual-comb spectroscopy (DCS), converting spectral information in the optical frequency domain to the audio frequency domain via multi-heterodyne beating, enables background-free spectral measurements with high resolution and broad bandwidth. However, the detection sensitivity remains limited due to the low power of individual comb lines and the lack of broadband acoustic resonators. Here, we develop cavity-enhanced photoacoustic DCS, which overcomes these limitations by using a high-finesse optical cavity for the power amplification of dual-frequency combs and a broadband acoustic resonator with a flat-top frequency response. We demonstrate high-resolution spectroscopic measurements of trace amounts of C2H2, NH3 and CO in the entire telecommunications C-band. The method shows a minimum detection limit of 0.6 ppb C2H2 at the measurement time of 100 s, corresponding to the noise equivalent absorption coefficient of 7 × 10−10 cm−1. The proposed cavity-enhanced photoacoustic DCS may open new avenues for ultrasensitive, high-resolution, and multi-species gas detection with widespread applications.
The role of inflammasomes in human diseases and their potential as therapeutic targets
Authors: Yao Jing , Sterling Keenan , Wang Zhe , Zhang Yun , Song Weihong
Published: January 2024

Inflammasomes are large protein complexes that play a major role in sensing inflammatory signals and triggering the innate immune response. Each inflammasome complex has three major components: an upstream sensor molecule that is connected to a downstream effector protein such as caspase-1 through the adapter protein ASC. Inflammasome formation typically occurs in response to infectious agents or cellular damage. The active inflammasome then triggers caspase-1 activation, followed by the secretion of pro-inflammatory cytokines and pyroptotic cell death. Aberrant inflammasome activation and activity contribute to the development of diabetes, cancer, and several cardiovascular and neurodegenerative disorders. As a result, recent research has increasingly focused on investigating the mechanisms that regulate inflammasome assembly and activation, as well as the potential of targeting inflammasomes to treat various diseases. Multiple clinical trials are currently underway to evaluate the therapeutic potential of several distinct inflammasome-targeting therapies. Therefore, understanding how different inflammasomes contribute to disease pathology may have significant implications for developing novel therapeutic strategies. In this article, we provide a summary of the biological and pathological roles of inflammasomes in health and disease. We also highlight key evidence that suggests targeting inflammasomes could be a novel strategy for developing new disease-modifying therapies that may be effective in several conditions.
The efficacy of various irrigation techniques on the removal of double antibiotic paste from simulated immature roots and the amount of apically extruded debris
Authors: Nasr El-Din Shaimaa , Hassan Reham
Published: January 2024

Objective

This study evaluated the effect of the XP-Endo Finisher (XPF), passive ultrasonic irrigation (PUI) and conventional irrigation using side-vented needle (SVN) on the amount of apically extruded debris and canal cleanliness following the removal of double antibiotic paste (DAP) from immature root canal models.

Material and methods

Forty-eight extracted mandibular premolars were drilled using peeso drills to simulate immature apices. The canals were filled with DAP and were randomly assigned into 3 groups according to the DAP removal method: XPF, PUI, and SVN (n = 16). The amount of extruded debris was assessed with an analytical balance then roots were split longitudinally and imaged using stereomicroscope to evaluate the residual medicament. Data were statistically analyzed using Kruskal-Wallis and Dunn’s test. Spearman’s correlation coefficient was used to determine significant correlation between extruded debris and the residual DAP scores.

Results

There was no significant difference between debris extrusion values for all groups (P value 0.237). For canal cleanliness, the amount of remaining DAP was significantly lower in the XPF and PUI compared to SVN (P value < 0.001). A non-significant positive (direct) correlation was found between the amounts of apically extruded debris and residual DAP scores (P value 0.087).

Conclusion

XPF and PUI were associated with better canal cleanliness during removal of DAP, no difference could be found between the three irrigation techniques regarding the debris extrusion.
Novel dual inhibitors of PARP and HDAC induce intratumoral STING-mediated antitumor immunity in triple-negative breast cancer
Authors: Zhu Qingyun , Dai Qiuzi , Zhao Lei , Zheng Chang , Li Qinyuan , Yuan Zigao , Li Lulu , Xie Zhuoye , Qiu Zixuan , Huang Wenjun , Liu Guowen , Zu Xuyu , Chu Bizhu , Jiang Yuyang
Published: January 2024

PARP inhibitors and HDAC inhibitors have been approved for the clinical treatment of malignancies, but acquired resistance of or limited effects on solid tumors with a single agent remain as challenges. Bioinformatics analyses and a combination of experiments had demonstrated the synergistic effects of PARP and HDAC inhibitors in triple-negative breast cancer. A series of novel dual PARP and HDAC inhibitors were rationally designed and synthesized, and these molecules exhibited high enzyme inhibition activity with excellent antitumor effects in vitro and in vivo. Mechanistically, dual PARP and HDAC inhibitors induced BRCAness to restore synthetic lethality and promoted cytosolic DNA accumulation, which further activates the cGAS–STING pathway and produces proinflammatory chemokines through type I IFN-mediated JAK–STAT pathway. Moreover, these inhibitors promoted neoantigen generation, upregulated antigen presentation genes and PD-L1, and enhanced antitumor immunity when combined with immune checkpoint blockade therapy. These results indicated that novel dual PARP and HDAC inhibitors have antitumor immunomodulatory functions in triple-negative breast cancer.
CLIC3 interacts with NAT10 to inhibit N4-acetylcytidine modification of p21 mRNA and promote bladder cancer progression
Authors: Shuai Yujun , Zhang Hui , Liu Changhao , Wang Junting , Jiang Yangkai , Sun Jiayin , Gao Xincheng , Bo Xiaochen , Xiao Xingyuan , Liao Xin , Huang Chao , Chen Hebing , Jiang Guosong
Published: January 2024

Chromatin accessibility plays important roles in revealing the regulatory networks of gene expression, while its application in bladder cancer is yet to be fully elucidated. Chloride intracellular channel 3 (CLIC3) protein has been reported to be associated with the progression of some tumors, whereas the specific mechanism of CLIC3 in tumor remains unclear. Here, we screened for key genes in bladder cancer through the identification of transcription factor binding site clustered region (TFCR) on the basis of chromatin accessibility and TF motif. CLIC3 was identified by joint profiling of chromatin accessibility data with TCGA database. Clinically, CLIC3 expression was significantly elevated in bladder cancer and was negatively correlated with patient survival. CLIC3 promoted the proliferation of bladder cancer cells by reducing p21 expression in vitro and in vivo. Mechanistically, CLIC3 interacted with NAT10 and inhibited the function of NAT10, resulting in the downregulation of ac4C modification and stability of p21 mRNA. Overall, these findings uncover an novel mechanism of mRNA ac4C modification and CLIC3 may act as a potential therapeutic target for bladder cancer.
Effects of methionine deficiency on B7H3-DAP12-CAR-T cells in the treatment of lung squamous cell carcinoma
Authors: Yu Tao , Nie Feng-Qi , Zhang Qi , Yu Shao-Kun , Zhang Mei-Ling , Wang Qian , Wang En-Xiu , Lu Kai-Hua , Sun Ming
Published: January 2024

Lung squamous cell carcinoma (LUSC) is a subtype of lung cancer for which precision therapy is lacking. Chimeric antigen receptor T-cells (CAR-T) have the potential to eliminate cancer cells by targeting specific antigens. However, the tumor microenvironment (TME), characterized by abnormal metabolism could inhibit CAR-T function. Therefore, the aim of this study was to improve CAR-T efficacy in solid TME by investigating the effects of amino acid metabolism. We found that B7H3 was highly expressed in LUSC and developed DAP12-CAR-T targeting B7H3 based on our previous findings. When co-cultured with B7H3-overexpressing LUSC cells, B7H3-DAP12-CAR-T showed significant cell killing effects and released cytokines including IFN-γ and IL-2. However, LUSC cells consumed methionine (Met) in a competitive manner to induce a Met deficiency. CAR-T showed suppressed cell killing capacity, reduced cytokine release and less central memory T phenotype in medium with lower Met, while the exhaustion markers were up-regulated. Furthermore, the gene NKG7, responsible for T cell cytotoxicity, was downregulated in CAR-T cells at low Met concentration due to a decrease in m5C modification. NKG7 overexpression could partially restore the cytotoxicity of CAR-T in low Met. In addition, the anti-tumor efficacy of CAR-T was significantly enhanced when co-cultured with SLC7A5 knockdown LUSC cells at low Met concentration. In conclusion, B7H3 is a prospective target for LUSC, and B7H3-DAP12-CAR-T cells are promising for LUSC treatment. Maintaining Met levels in CAR-T may help overcome TME suppression and improve its clinical application potential.