bluuebunny/crossref_metadata_2025 huggingface dataset:
Study on endotoxin in indoor environment: research at equine-related facilities in Japan
Authors: Ogasawara Takeshi , Kim Hoon , Lim Eunsu
Published: January 2024

In recent years, endotoxins have received considerable attention as substances associated with allergic diseases. Endotoxins are cell wall components of gram-negative bacteria that are widely present in the living environment. Endotoxin concentrations are particularly high in environments where animals are housed. However, while the status of endotoxin concentrations in the general environment is becoming clearer, there remains a scarcity of studies in environments with potentially higher concentrations.

In this study, we measured indoor endotoxin concentrations in buildings in Japan that are strongly associated with horses. The target buildings include a “Magariya,” an old Japanese house, an accommodation facility connected to a horse stable, and a stable specifically for thoroughbreds. Air and dust samples were collected at these measurement targets and analyzed for air and dust concentrations.

Airborne concentrations were higher in buildings with horses present than in buildings without horses, and the presence/absence of horses is thought to have a significant effect on the airborne concentration of endotoxin. Additionally, as the density of horses increases, endotoxin concentrations also tend to increase. Dust concentration had different values in different rooms even in the same building. These results suggest that dust concentrations may be affected by floor materials, frequency of cleaning, and frequency of human traffic from areas of high concentrations. Endotoxin concentrations were high in the stable during the work because of the replacement of the dried straw in the stalls and the removal of horse excrement. These results are expected to be useful in controlling endotoxin concentrations in indoor environments of various building types.
Species discrimination in the multituberculate Mesodma Jepsen, 1940 (Mammalia, Allotheria): considerations of size, shape, and form
Authors: Ashbaugh Austin J. , Scott Craig S. , Wilson Mantilla Gregory P. , Theodor Jessica M.
Published: January 2024

Although knowledge of their fossil record continues to improve, multituberculates nonetheless remain one of the more poorly understood mammalian clades, which can be attributed to a record comprised of isolated teeth and fragmentary jaws. Fortunately, the p4 of multituberculates is the most common form of remains for this group and is a principal source of diagnostic characters in systematic studies, the p4 of cimolodontan multituberculates is both common and a source of diagnostic characters in systematic studies. The results of a recent morphometric study on the neoplagiaulacid Mesodma suggest that p4 size may be more useful than shape in diagnosing the various species referred to this genus. We tested this hypothesis by applying two different morphometric methods (2D geometric morphometrics and linear measurements) to two samples: (1) one including the p4s of four known species of Mesodma (M. ambigua, M. thompsoni, M. formosa, and M. pygmaea), and (2) a sample of unidentified p4s of Mesodma from the Bug Creek Anthills locality of northeastern Montana. Our results indicate that while form explains most of the morphological variation in p4s of the various species of Mesodma, linear-measurement data support differences in p4 morphology that are not recovered by form data alone. Depending on the methods used, we found evidence for the presence of one or more species of Mesodma in the Bug Creek Anthills fauna. Although shape and size both contribute to morphological variation in the p4 of Mesodma, our results suggest that the diagnostic power of each varies with the type of methodology employed.
PARTITION OF LARGE SUBSETS OF SEMIGROUPS
Authors: ZHANG TENG
Published: January 2024

It is known that in an infinite very weakly cancellative semigroup with size

$\kappa $

, any central set can be partitioned into

$\kappa $

central sets. Furthermore, if

$\kappa $

contains

$\lambda $

almost disjoint sets, then any central set contains

$\lambda $

almost disjoint central sets. Similar results hold for thick sets, very thick sets and piecewise syndetic sets. In this article, we investigate three other notions of largeness: quasi-central sets, C-sets, and J-sets. We obtain that the statement applies for quasi-central sets. If the semigroup is commutative, then the statement holds for C-sets. Moreover, if

$\kappa ^\omega = \kappa $

, then the statement holds for J-sets.
Glacier fluctuation chronology since the latest Pleistocene at Mount Rainier, Washington, USA
Authors: Samolczyk Mary , Osborn Gerald , Menounos Brian , Clark Douglas , Davis P. Thompson , Clague John J. , Koch Johannes
Published: January 2024

Large stratovolcanoes in the Cascade Range have high equilibrium-line altitudes that support glaciers whose Holocene and latest Pleistocene advances are amenable to dating. Glacier advances produced datable stratigraphic sequences in lateral moraines, which complement dating of end moraines. New mapping of glacial deposits on Mount Rainier using LIDAR and field observations supports a single latest Pleistocene or early Holocene advance. Rainier R tephra overlies deposits from this advance and could be as old as >11.6 ka; the advance could be of Younger Dryas age. Radiocarbon ages on wood interbedded between tills in the lateral moraines of Nisqually, Carbon, and Emmons glaciers and the South Tahoma glacier forefield suggest glacier advances between 200 and 550 CE, correlative with the First Millennium Advance in western Canada, and during the Little Ice Age (LIA) beginning as early as 1300 CE.

These results resolve previous contradictory interpretations of Mount Rainier's glacial history and indicate that the original proposal of a single pre-Neoglacial cirque advance is correct, in contrast to a later interpretation of two advances of pre- and post-Younger Dryas age, respectively. Meanwhile, the occurrence of the pre-LIA Burroughs Mountain Advance, interpreted in previous work as occurring 3–2.5 ka, is questionable based on inherently ambiguous interpretations of tephra distribution.
Pyrroloquinoline quinone supplementation attenuates inflammatory liver injury by STAT3/TGF-β1 pathway in weaned piglets challenged with lipopolysaccharide
Authors: Huang Caiyun , Yu Xuanci , Shi Chenyu , Wang Mengshi , Li Ang , Wang Fenglai
Published: January 2024

This study is aimed to evaluate the effect and underling mechanism of dietary supplementation with pyrroloquinoline quinone (PQQ) disodium on improving inflammatory liver injury in piglets challenged with lipopolysaccharide (LPS). A total of seventy-two crossbred barrows were allotted into four groups as follows: the CTRL group (basal diet + saline injection); the PQQ group (3 mg/kg PQQ diet + saline injection); the CTRL + LPS group (basal diet + LPS injection) and the PQQ + LPS group (3 mg/kg PQQ diet + LPS injection). On days 7, 11 and 14, piglets were challenged with LPS or saline. Blood was sampled at 4 h after the last LPS injection (day 14), and then the piglets were slaughtered and liver tissue was harvested. The results showed that the hepatic morphology was improved in the PQQ + LPS group compared with the CTRL + LPS group. PQQ supplementation decreased the level of serum inflammatory factors, aspartate aminotransferase and alanine transaminase, and increased the HDL-cholesterol concentration in piglets challenged with LPS; piglets in the PQQ + LPS group had lower liver mRNA level of inflammatory factors and protein level ofα-smooth muscle actin than in the CTRL + LPS group. Besides, mRNA expression of STAT3/TGF-β1 pathway and protein level of p-STAT3(Tyr 705) were decreased, and mRNA level ofPPARαand protein expression of p-AMPK in liver were increased in the PQQ + LPS group compared with the CTRL + LPS group (P< 0·05). In conclusion, dietary supplementation with PQQ alleviated inflammatory liver injury might partly via inhibition of the STAT3/TGF-β1 pathway in piglets challenged with LPS.
Carl Schmitt's Multifaceted Rejection of Political Compromises
Authors: Baume Sandrine
Published: January 2024

Carl Schmitt's constant denunciation of political compromises has received little attention. This omission is damaging in two ways. On the one hand, it misses a central aspect of Schmitt's political thought. On the other, it deprives those interested in discourses challenging the legitimacy of compromise in democracy of a valuable source. In this article, I systematize Schmitt's multifaceted grievances to compromises, especially as expressed in the 1920s and early 1930s. If the Weimar Constitution is fertile soil for observing and contesting compromises, the Third Reich constituted, for Schmitt, a paradigm reversal on this subject, as it managed to rid itself of pluralism and compromises. Schmitt has been portrayed as an authoritarian populist: the systematic reconstruction of his critique of compromise allows for a finer elaboration of the points of convergence and divergence between his democratic theory and populist views of democracy.
Overcoming major barriers in seed ecology research in developing countries
Authors: Silveira Fernando A. O. , Fuzessy Lisieux , Phartyal Shyam S. , Dayrell Roberta L. C. , Vandelook Filip , Vázquez-Ramírez Jerónimo , Tavşanoğlu Çağatay , Abedi Mehdi , Naidoo Sershen , Acosta-Rojas Diana C. , Chen Si-Chong , Cruz-Tejada Diana M. , Jayasuryia Gehan , Ordóñez-Parra Carlos A. , Saatkamp Arne
Published: January 2024

Scientists are becoming increasingly aware that disparities in opportunities for conducting and publishing research among scientists living under different socio-economic contexts have created pervasive biases and long-lasting impacts on our views of the natural world. These disparities are challenging the establishment of a global research agenda for a variety of disciplines, including seed ecology. Seed ecology has progressed enormously recently, but multiple barriers have hindered progress in the Global South where biodiversity and environmental complexity are highest. Here, we identify ten major challenges that seed ecologists from developing countries face in relation to planning, designing, conducting and publishing their research. We also propose several measures to overcome these challenges: (1) closing biodiversity knowledge shortfalls, (2) enhancing and creating long-term seed ecological networks, (3) supporting better infrastructure, (4) making fieldwork easier and safer, (5) unlocking funding opportunities, (6) promoting inclusive scientific meetings, (7) alleviating language barriers, (8) improving education, (9) shifting the notion of novelty and relevance and (10) supporting native seed markets. The authors recommend that the proposed solutions can be implemented by seed ecologists and the broader scientific community including funding agencies, research directors, journal editors and the academic publishing industry. Solutions can help mitigate multiple challenges simultaneously, thus offering a relatively inexpensive, fast and productive pathway for the development of seed ecology into a truly global research discipline that benefits scientists irrespective of their geographic location and background.
Different Culture, Same Situation? Translating and Applying a Situational Judgment Test From Germany in Cuba
Authors: Schäpers Philipp , Heinemann Henrik , Alvarez Daybel Pañellas , Nohr Laura , Mönke Franz W.
Published: January 2024

Abstract: Situational judgment tests (SJTs) are popular instruments in selection and assessment. However, the application of SJTs to non-Western cultural contexts remains scarce. In this study, we investigated whether an SJT on personal initiative, developed in Germany and translated into Cuban Spanish, had similar psychometric properties in Cuba. Second, there is an ongoing debate about the extent to which the situation description plays an important role for SJTs. We supposed that the impact of situation descriptions might depend on test takers’ familiarity with the culture in which the SJT was developed. Hence, we tested whether the omission of situation descriptions had larger effects in a Cuban than in a German sample. We applied a 2 (with vs. without situation description in the item stem) × 2 (cultural background: Cuba vs. Germany) between-subjects design ( NCuba = 192, NGermany = 213). The results revealed similar psychometric properties between Cuban and German test takers concerning measurement invariance, construct-related validity, and reliability. In addition, we examined whether samples differ regarding applicant perceptions: Notably, for four of six applicant perception scales, the Cuban sample reported a more positive view of the SJT. Furthermore, we found that the effect of situation availability on SJT performance did not substantially depend on the test takers’ cultural background. Implications for cross-cultural generalizability are discussed.
Climatology of Martian Ionospheric Disturbances Deduced From MAVEN Data in 2014–2023
Authors: Park Jaeheung
Published: January 2024

We investigate the climatology of Martian ionospheric disturbances using Mars Atmosphere and Volatile Evolution missioN (MAVEN) data in 2014–2023. The disturbance strength is estimated by calculating residuals of in situ density from its large‐scale (filter window size ∼560 km) background and normalizing the residual with the background, as has been commonly used in terrestrial aeronomy. The disturbances are statistically stronger (a) in the local winter hemisphere than in summer and (b) on the nightside than on the dayside, with stark contrast across the terminator. The disturbances are more intense over the regions with strong radial magnetic fields (i.e., Martian crustal anomaly) than at unmagnetized regions, especially during the nighttime. Day‐to‐day variability of the Martian ionospheric disturbances does not exhibit a strong correlation with those of thermospheric CO2 disturbances or solar wind electron density/temperature at Mars.
A natural biogenic nanozyme for scavenging superoxide radicals
Authors: Ma Long , Zheng Jia-Jia , Zhou Ning , Zhang Ruofei , Fang Long , Yang Yili , Gao Xingfa , Chen Chunying , Yan Xiyun , Fan Kelong
Published: January 2024

Biominerals, the inorganic minerals of organisms, are known mainly for their physical property-related functions in modern living organisms. Our recent discovery of the enzyme-like activities of nanomaterials, coined as nanozyme, inspires the hypothesis that nano-biominerals might function as enzyme-like catalyzers in cells. Here we report that the iron cores of biogenic ferritins act as natural nanozymes to scavenge superoxide radicals. Through analyzing eighteen representative ferritins from three living kingdoms, we find that the iron core of prokaryote ferritin possesses higher superoxide-diminishing activity than that of eukaryotes. Further investigation reveals that the differences in catalytic capability result from the iron/phosphate ratio changes in the iron core, which is mainly determined by the structures of ferritins. The phosphate in the iron core switches the iron core from single crystalline to amorphous iron phosphate-like structure, resulting in decreased affinity to the hydrogen proton of the ferrihydrite-like core that facilitates its reaction with superoxide in a manner different from that of ferric ions. Furthermore, overexpression of ferritins with high superoxide-diminishing activities in E. coli increases the resistance to superoxide, whereas bacterioferritin knockout or human ferritin knock-in diminishes free radical tolerance, highlighting the physiological antioxidant role of this type of nanozymes.
Diversifying crop rotation increases food production, reduces net greenhouse gas emissions and improves soil health
Authors: Yang Xiaolin , Xiong Jinran , Du Taisheng , Ju Xiaotang , Gan Yantai , Li Sien , Xia Longlong , Shen Yanjun , Pacenka Steven , Steenhuis Tammo S. , Siddique Kadambot H. M. , Kang Shaozhong , Butterbach-Bahl Klaus
Published: January 2024

Global food production faces challenges in balancing the need for increased yields with environmental sustainability. This study presents a six-year field experiment in the North China Plain, demonstrating the benefits of diversifying traditional cereal monoculture (wheat–maize) with cash crops (sweet potato) and legumes (peanut and soybean). The diversified rotations increase equivalent yield by up to 38%, reduce N2O emissions by 39%, and improve the system’s greenhouse gas balance by 88%. Furthermore, including legumes in crop rotations stimulates soil microbial activities, increases soil organic carbon stocks by 8%, and enhances soil health (indexed with the selected soil physiochemical and biological properties) by 45%. The large-scale adoption of diversified cropping systems in the North China Plain could increase cereal production by 32% when wheat–maize follows alternative crops in rotation and farmer income by 20% while benefiting the environment. This study provides an example of sustainable food production practices, emphasizing the significance of crop diversification for long-term agricultural resilience and soil health.
Reorganization of intrinsic functional connectivity in early-stage Parkinson’s disease patients with probable REM sleep behavior disorder
Authors: Dan Xiao-Juan , Wang Yu-Wei , Sun Jun-Yan , Gao Lin-Lin , Chen Xiao , Yang Xue-Ying , Xu Er-He , Ma Jing-Hong , Yan Chao-Gan , Wu Tao , Chan Piu
Published: January 2024

REM sleep behavior disorder (RBD) symptoms in Parkinson’s disease (PD) suggest both a clinically and pathologically malignant subtype. However, whether RBD symptoms are associated with alterations in the organization of whole-brain intrinsic functional networks in PD, especially at early disease stages, remains unclear. Here we use resting-state functional MRI, coupled with graph-theoretical approaches and network-based statistics analyses, and validated with large-scale network analyses, to characterize functional brain networks and their relationship with clinical measures in early PD patients with probable RBD (PD+pRBD), early PD patients without probable RBD (PD-pRBD) and healthy controls. Thirty-six PD+pRBD, 57 PD-pRBD and 71 healthy controls were included in the final analyses. The PD+pRBD group demonstrated decreased global efficiency (t = -2.036, P = 0.0432) compared to PD-pRBD, and decreased network efficiency, as well as comprehensively disrupted nodal efficiency and whole-brain networks (all eight networks, but especially in the sensorimotor, default mode and visual networks) compared to healthy controls. The PD-pRBD group showed decreased nodal degree in right ventral frontal cortex and more affected edges in the frontoparietal and ventral attention networks compared to healthy controls. Furthermore, the assortativity coefficient was negatively correlated with Montreal cognitive assessment scores in the PD+pRBD group (r = -0.365, P = 0.026, d = 0.154). The observation of altered whole-brain functional networks and its correlation with cognitive function in PD+pRBD suggest reorganization of the intrinsic functional connectivity to maintain the brain function in the early stage of the disease. Future longitudinal studies following these alterations along disease progression are warranted.
Transcriptomic profiling of early synucleinopathy in rats induced with preformed fibrils
Authors: Patterson Joseph R. , Kochmanski Joseph , Stoll Anna C. , Kubik Michael , Kemp Christopher J. , Duffy Megan F. , Thompson Kajene , Howe Jacob W. , Cole-Strauss Allyson , Kuhn Nathan C. , Miller Kathryn M. , Nelson Seth , Onyekpe Christopher U. , Beck John S. , Counts Scott E. , Bernstein Alison I. , Steece-Collier Kathy , Luk Kelvin C. , Sortwell Caryl E.
Published: January 2024

Examination of early phases of synucleinopathy when inclusions are present, but long before neurodegeneration occurs, is critical to both understanding disease progression and the development of disease modifying therapies. The rat alpha-synuclein (α-syn) preformed fibril (PFF) model induces synchronized synucleinopathy that recapitulates the pathological features of Parkinson’s disease (PD) and can be used to study synucleinopathy progression. In this model, phosphorylated α-syn (pSyn) inclusion-containing neurons and reactive microglia (major histocompatibility complex-II immunoreactive) peak in the substantia nigra pars compacta (SNpc) months before appreciable neurodegeneration. However, it remains unclear which specific genes are driving these phenotypic changes. To identify transcriptional changes associated with early synucleinopathy, we used laser capture microdissection of the SNpc paired with RNA sequencing (RNASeq). Precision collection of the SNpc allowed for the assessment of differential transcript expression in the nigral dopamine neurons and proximal glia. Transcripts upregulated in early synucleinopathy were mainly associated with an immune response, whereas transcripts downregulated were associated with neurotransmission and the dopamine pathway. A subset of 29 transcripts associated with neurotransmission/vesicular release and the dopamine pathway were verified in a separate cohort of males and females to confirm reproducibility. Within this subset, fluorescent in situ hybridization (FISH) was used to localize decreases in the Syt1 and Slc6a3 transcripts to pSyn inclusion-containing neurons. Identification of transcriptional changes in early synucleinopathy provides insight into the molecular mechanisms driving neurodegeneration.
Different effect of hypo- and hypermetabolism on cognition in dementia with Lewy bodies: are they coupled or independent?
Authors: Jeong Seong Ho , Cha Jungho , Yoo Han Soo , Chung Seok Jong , Jung Jin Ho , Sohn Young H. , Lee Phil Hyu
Published: January 2024

Patients with dementia with Lewy bodies (DLB) show widespread brain metabolic changes. This study investigated whether brain hypo- and hypermetabolism in DLB have differential effects on cognition. We enrolled 55 patients with DLB (15 prodromal DLB [MCI-LB] and 40 probable DLB) and 13 healthy controls who underwent 18F-fluorodeoxyglucose positron emission tomography and detailed neuropsychological tests. Metabolic indices reflecting associated changes in regional cerebral glucose metabolism were calculated as follows: index(-) for hypometabolism [DLB-hypo] and index(+) for hypermetabolism [DLB-hyper]. The effects of DLB-hypo or DLB-hyper on cognitive function were assessed using a multivariate linear regression model. Additionally, a linear mixed model was used to investigate the association between each index and the longitudinal cognitive decline. There was no correlation between DLB-hypo and DLB-hyper in the disease group. The multivariate linear regression model showed that DLB-hypo was associated with language, visuospatial, visual memory, and frontal/executive functions; whereas DLB-hyper was responsible for attention and verbal memory. There was significant interaction between DLB-hypo and DLB-hyper for verbal and visual memory, which was substantially affected by DLB-hyper in relatively preserved DLB-hypo status. A linear mixed model showed that DLB-hypo was associated with longitudinal cognitive outcomes, regardless of cognitive status, and DLB-hyper contributed to cognitive decline only in the MCI-LB group. The present study suggests that DLB-hypo and DLB-hyper may be independent of each other and differentially affect the baseline and longitudinal cognitive function in patients with DLB.
Periodicity staircase in a centrosymmetric Fe/Gd magnetic thin film system
Authors: Singh Arnab , Li Junli , Montoya Sergio A. , Morley Sophie , Fischer Peter , Kevan Steve D. , Fullerton Eric E. , Yao Dao-Xin , Datta Trinanjan , Roy Sujoy
Published: January 2024

The presence of multiple competing periodicities may result in a system to go through states with modulated periodicities, an example of which is the self-similar staircase-like structure called the Devil’s Staircase. Herein we report on a novel staircase structure of domain periodicity in an amorphous and centrosymmetric Fe/Gd magnetic thin film system wherein the reciprocal space wavevector Q due to the ordered stripe domains does not evolve continuously, rather exhibits a staircase structure. Resonant X-ray scattering experiments show jumps in the periodicity of the stripe domains as a function of an external magnetic field. When resolved in components, the length-scale step change along Qx was found to be an integral multiple of a minimum step height of 7 nm, which resembles closely to the exchange length of the system. Modeling the magnetic texture in the Fe/Gd system as an achiral spin arrangement, we have been able to reproduce the steps in the magnetization using a Landau-Lifshitz spin dynamics calculation. Our results indicate that anisotropy and not the dipolar interaction is the dominant cause for the staircase pattern, thereby revealing the effect of achiral magnetism.
Leaf microbiome dysbiosis triggered by T2SS-dependent enzyme secretion from opportunistic Xanthomonas pathogens
Authors: Pfeilmeier Sebastian , Werz Anja , Ote Marine , Bortfeld-Miller Miriam , Kirner Pascal , Keppler Andreas , Hemmerle Lucas , Gäbelein Christoph G. , Petti Gabriella C. , Wolf Sarah , Pestalozzi Christine M. , Vorholt Julia A.
Published: January 2024

In healthy plants, the innate immune system contributes to maintenance of microbiota homoeostasis, while disease can be associated with microbiome perturbation or dysbiosis, and enrichment of opportunistic plant pathogens like Xanthomonas. It is currently unclear whether the microbiota change occurs independently of the opportunistic pathogens or is caused by the latter. Here we tested if protein export through the type-2 secretion system (T2SS) by Xanthomonas causes microbiome dysbiosis in Arabidopsis thaliana in immunocompromised plants. We found that Xanthomonas strains secrete a cocktail of plant cell wall-degrading enzymes that promote Xanthomonas growth during infection. Disease severity and leaf tissue degradation were increased in A. thaliana mutants lacking the NADPH oxidase RBOHD. Experiments with gnotobiotic plants, synthetic bacterial communities and wild-type or T2SS-mutant Xanthomonas revealed that virulence and leaf microbiome composition are controlled by the T2SS. Overall, a compromised immune system in plants can enrich opportunistic pathogens, which damage leaf tissues and ultimately cause microbiome dysbiosis by facilitating growth of specific commensal bacteria.
3D nanofabricated soft microrobots with super-compliant picoforce springs as onboard sensors and actuators
Authors: Xu Haifeng , Wu Song , Liu Yuan , Wang Xiaopu , Efremov Artem K. , Wang Lei , McCaskill John S. , Medina-Sánchez Mariana , Schmidt Oliver G.
Published: January 2024

Microscale organisms and specialized motile cells use protein-based spring-like responsive structures to sense, grasp and move. Rendering this biomechanical transduction functionality in an artificial micromachine for applications in single-cell manipulations is challenging due to the need for a bio-applicable nanoscale spring system with a large and programmable strain response to piconewton-scale forces. Here we present three-dimensional nanofabrication and monolithic integration, based on an acrylic elastomer photoresist, of a magnetic spring system with quantifiable compliance sensitive to 0.5 pN, constructed with customized elasticity and magnetization distributions at the nanoscale. We demonstrate the effective design programmability of these ‘picospring’ ensembles as energy transduction mechanisms for the integrated construction of customized soft micromachines, with onboard sensing and actuation functions at the single-cell scale for microrobotic grasping and locomotion. The integration of active soft springs into three-dimensional nanofabrication offers an avenue to create biocompatible soft microrobots for non-disruptive interactions with biological entities.
Inferring neural activity before plasticity as a foundation for learning beyond backpropagation
Authors: Song Yuhang , Millidge Beren , Salvatori Tommaso , Lukasiewicz Thomas , Xu Zhenghua , Bogacz Rafal
Published: January 2024

For both humans and machines, the essence of learning is to pinpoint which components in its information processing pipeline are responsible for an error in its output, a challenge that is known as ‘credit assignment’. It has long been assumed that credit assignment is best solved by backpropagation, which is also the foundation of modern machine learning. Here, we set out a fundamentally different principle on credit assignment called ‘prospective configuration’. In prospective configuration, the network first infers the pattern of neural activity that should result from learning, and then the synaptic weights are modified to consolidate the change in neural activity. We demonstrate that this distinct mechanism, in contrast to backpropagation, (1) underlies learning in a well-established family of models of cortical circuits, (2) enables learning that is more efficient and effective in many contexts faced by biological organisms and (3) reproduces surprising patterns of neural activity and behavior observed in diverse human and rat learning experiments.
PRMT5 inhibition shows in vitro efficacy against H3K27M-altered diffuse midline glioma, but does not extend survival in vivo
Authors: Brown Elizabeth J. , Balaguer-Lluna Leire , Cribbs Adam P. , Philpott Martin , Campo Leticia , Browne Molly , Wong Jong Fu , Oppermann Udo , Carcaboso Ángel M. , Bullock Alex N. , Farnie Gillian
Published: January 2024

H3K27-altered Diffuse Midline Glioma (DMG) is a universally fatal paediatric brainstem tumour. The prevalent driver mutation H3K27M creates a unique epigenetic landscape that may also establish therapeutic vulnerabilities to epigenetic inhibitors. However, while HDAC, EZH2 and BET inhibitors have proven somewhat effective in pre-clinical models, none have translated into clinical benefit due to either poor blood–brain barrier penetration, lack of efficacy or toxicity. Thus, there remains an urgent need for new DMG treatments. Here, we performed wider screening of an epigenetic inhibitor library and identified inhibitors of protein arginine methyltransferases (PRMTs) among the top hits reducing DMG cell viability. Two of the most effective inhibitors, LLY-283 and GSK591, were targeted against PRMT5 using distinct binding mechanisms and reduced the viability of a subset of DMG cells expressing wild-type TP53 and mutant ACVR1. RNA-sequencing and phenotypic analyses revealed that LLY-283 could reduce the viability, clonogenicity and invasion of DMG cells in vitro, representing three clinically important phenotypes, but failed to prolong survival in an orthotopic xenograft model. Together, these data show the challenges of DMG treatment and highlight PRMT5 inhibitors for consideration in future studies of combination treatments.
Assessing hypo-arousal during reward anticipation with pupillometry in patients with major depressive disorder: replication and correlations with anhedonia
Authors: Brendler Andy , Schneider Max , Elbau Immanuel G. , Sun Rui , Nantawisarakul Taechawidd , Pöhlchen Dorothee , Brückl Tanja ,   BeCOME Working Group, Brem A. K. , Binder E. B. , Erhardt A. , Fietz J. , Grandi N. C. , Kim Y. , Ilić-Ćoćić S. , Leuchs L. , Lucae S. , Namendorf T. , Pape J. , Schilbach L. , von Mücke-Heim I. , Ziebula J. , Czisch Michael , Sämann Philipp G. , Lee Michael D. , Spoormaker Victor I.
Published: January 2024

Major depressive disorder (MDD) is a devastating and heterogenous disorder for which there are no approved biomarkers in clinical practice. We recently identified anticipatory hypo-arousal indexed by pupil responses as a candidate mechanism subserving depression symptomatology. Here, we conducted a replication and extension study of these findings. We analyzed a replication sample of 40 unmedicated patients with a diagnosis of depression and 30 healthy control participants, who performed a reward anticipation task while pupil responses were measured. Using a Bayesian modelling approach taking measurement uncertainty into account, we could show that the negative correlation between pupil dilation and symptom load during reward anticipation is replicable within MDD patients, albeit with a lower effect size. Furthermore, with the combined sample of 136 participants (81 unmedicated depressed and 55 healthy control participants), we further showed that reduced pupil dilation in anticipation of reward is inversely associated with anhedonia items of the Beck Depression Inventory in particular. Moreover, using simultaneous fMRI, particularly the right anterior insula as part of the salience network was negatively correlated with depressive symptom load in general and anhedonia items specifically. The present study supports the utility of pupillometry in assessing noradrenergically mediated hypo-arousal during reward anticipation in MDD, a physiological process that appears to subserve anhedonia.
Diagnostic performance of wide-field optical coherence tomography angiography for high myopic glaucoma
Authors: Hong Rim Kyung , Kim Ji Hong , Toh Gyungmin , Na Kyeong Ik , Seong Mincheol , Lee Won June
Published: January 2024

Diagnosing and monitoring glaucoma in high myopic (HM) eyes are becoming very important; however, it is challenging to diagnose this condition. This study aimed to evaluate the diagnostic ability of wide-field optical coherence tomography angiography (WF-OCTA) maps for the detection of glaucomatous damage in eyes with HM and to compare the diagnostic ability of WF-OCTA maps with that of conventional imaging approaches, including swept-source optical coherence tomography (SS-OCT) wide-field maps. In this retrospective observational study, a total 62 HM-healthy eyes and 140 HM eyes with open-angle glaucoma were included. Patients underwent a comprehensive ocular examination, including SS-OCT wide-field and 12 × 12 WF-OCTA scans. The WF-OCTA map represents the peripapillary and macular superficial vascular density maps. Glaucoma specialists determined the presence of glaucomatous damage in HM eyes by reading the WF-OCTA map and comparing its sensitivity and specificity with those of conventional SS-OCT images. The sensitivity and specificity of 12 × 12 WF-OCTA scans for HM-glaucoma diagnosis were 87.28% and 86.94%, respectively, while, the sensitivity and specificity of SS-OCT wide-field maps for HM-glaucoma diagnosis were 87.49% and 80.51%, respectively. The specificity of the WF-OCTA map was significantly higher than that of the SS-OCT wide-field map (p < 0.05). The sensitivity of the WF-OCTA map was comparable with that of the SS-OCT wide-field map (p = 0.078). The WF-OCTA map showed good diagnostic ability for discriminating HM-glaucomatous eyes from HM-healthy eyes. As a complementary method to an alternative imaging modality, WF-OCTA mapping can be a useful tool for the detection of HM glaucoma.
Deep learning-based prediction of in-hospital mortality for sepsis
Authors: Yong Li , Zhenzhou Liu
Published: January 2024

As a serious blood infection disease, sepsis is characterized by a high mortality risk and many complications. Accurate assessment of mortality risk of patients with sepsis can help physicians in Intensive Care Unit make optimal clinical decisions, which in turn can effectively save patients’ lives. However, most of the current clinical models used for assessing mortality risk in sepsis patients are based on conventional indicators. Unfortunately, some of the conventional indicators have been shown to be inapplicable in the accurate clinical diagnosis nowadays. Meanwhile, traditional evaluation models only focus on a small amount of personal data, causing misdiagnosis of sepsis patients. We refine the core indicators for mortality risk assessment of sepsis from massive clinical electronic medical records with machine learning, and propose a new mortality risk assessment model, DGFSD, for sepsis patients based on deep learning. The DGFSD model can not only learn individual clinical information about unassessed patients, but also obtain information about the structure of the similarity graph between diagnosed patients and patients to be assessed. Numerous experiments have shown that the accuracy of the DGFSD model is superior to baseline methods, and can significantly improve the efficiency of clinical auxiliary diagnosis.
HMGB1 mediates microbiome-immune axis dysregulation underlying reduced neutralization capacity in obesity-related post-acute sequelae of SARS-CoV-2
Authors: Rubas Noelle C. , Peres Rafael , Kunihiro Braden P. , Allan Nina P. , Phankitnirundorn Krit , Wells Riley K. , McCracken Trevor , Lee Rosa H. , Umeda Lesley , Conching Andie , Juarez Ruben , Maunakea Alika K.
Published: January 2024

While obesity is a risk factor for post-acute sequelae of SARS-CoV-2 infection (PASC, "long-COVID"), the mechanism(s) underlying this phenomenon remains poorly understood. To address this gap in knowledge, we performed a 6-week longitudinal study to examine immune activity and gut microbiome dysbiosis in post-acute stage patients recovering from SARS-CoV-2 infection. Self-reported symptom frequencies and blood samples were collected weekly, with plasma assessed by ELISA and Luminex for multiple biomarkers and immune cell profiling. DNA from stool samples were collected at the early stage of recovery for baseline assessments of gut microbial composition and diversity using 16S-based metagenomic sequencing. Multiple regression analyses revealed obesity-related PASC linked to a sustained proinflammatory immune profile and reduced adaptive immunity, corresponding with reduced gut microbial diversity. In particular, enhanced signaling of the high mobility group box 1 (HMGB1) protein was found to associate with this dysregulation, with its upregulated levels in plasma associated with significantly impaired viral neutralization that was exacerbated with obesity. These findings implicate HMGB1 as a candidate biomarker of PASC, with potential applications for risk assessment and targeted therapies.
Rapid artefact removal and H&E-stained tissue segmentation
Authors: Schreiber B. A. , Denholm J. , Jaeckle F. , Arends M. J. , Branson K. M. , Schönlieb C.-B. , Soilleux E. J.
Published: January 2024

We present an innovative method for rapidly segmenting haematoxylin and eosin (H&E)-stained tissue in whole-slide images (WSIs) that eliminates a wide range of undesirable artefacts such as pen marks and scanning artefacts. Our method involves taking a single-channel representation of a low-magnification RGB overview of the WSI in which the pixel values are bimodally distributed such that H&E-stained tissue is easily distinguished from both background and a wide variety of artefacts. We demonstrate our method on 30 WSIs prepared from a wide range of institutions and WSI digital scanners, each containing substantial artefacts, and compare it to segmentations provided by Otsu thresholding and Histolab tissue segmentation and pen filtering tools. We found that our method segmented the tissue and fully removed all artefacts in 29 out of 30 WSIs, whereas Otsu thresholding failed to remove any artefacts, and the Histolab pen filtering tools only partially removed the pen marks. The beauty of our approach lies in its simplicity: manipulating RGB colour space and using Otsu thresholding allows for the segmentation of H&E-stained tissue and the rapid removal of artefacts without the need for machine learning or parameter tuning.
Purpose reflection benefits minoritized students’ motivation and well-being in STEM
Authors: Diekman Amanda B. , Joshi Mansi P. , White Andrew D. , Tran Quang-Anh Ngo , Seth Jayshree
Published: January 2024

Students from groups historically excluded from STEM face heightened challenges to thriving and advancing in STEM. Prompting students to reflect on these challenges in light of their purpose can yield benefits by helping students see how their STEM work connects to fundamental motives. We conducted a randomized, controlled trial to test potential benefits of reflecting on purpose—their “why” for pursuing their degrees. This multimethod study included 466 STEM students (232 women; 237 Black/Latinx/Native students). Participants wrote about their challenges in STEM, with half randomly assigned to consider these in light of their purpose. Purpose reflection fostered benefits to beliefs and attitudes about the major, authentic belonging, and stress appraisals. Effects were robust across race and gender identities or larger for minoritized students. Structural and cultural shifts to recognize students’ purpose in STEM can provide a clearer pathway for students to advance.
Aryl-quinoline-4-carbonyl hydrazone bearing different 2-methoxyphenoxyacetamides as potent α-glucosidase inhibitors; molecular dynamics, kinetic and structure–activity relationship studies
Authors: Hamedifar Haleh , Mirfattahi Mahroo , Khalili Ghomi Minoo , Azizian Homa , Iraji Aida , Noori Milad , Moazzam Ali , Dastyafteh Navid , Nokhbehzaim Ali , Mehrpour Katayoun , Javanshir Shahrzad , Mojtabavi Somayeh , Faramarzi Mohammad Ali , Larijani Bagher , Hajimiri Mir Hamed , Mahdavi Mohammad
Published: January 2024

Regarding the important role of α-glucosidase enzyme in the management of type 2 diabetes mellitus, the current study was established to design and synthesize aryl-quinoline-4-carbonyl hydrazone bearing different 2-methoxyphenoxyacetamide (11a–o) and the structure of all derivatives was confirmed through various techniques including IR, 1H-NMR, 13C-NMR and elemental analysis. Next, the α-glucosidase inhibitory potentials of all derivatives were evaluated, and all compounds displayed potent inhibition with IC50 values in the range of 26.0 ± 0.8–459.8 ± 1.5 µM as compared to acarbose used as control, except 11f and 11l. Additionally, in silico-induced fit docking and molecular dynamics studies were performed to further investigate the interaction, orientation, and conformation of the newly synthesized compounds over the active site of α-glucosidase.
Identification of desalination and wind power plants sites using m-polar fuzzy Aczel–Alsina aggregation information
Authors: Rahman Zia Ur , Ali Ghous , Asif Muhammad , Chen Yufeng , Abidin Muhammad Zain Ul
Published: January 2024

Real-world decision-making problems often include multi-polar uncertainties dependent on multi-dimensional attributes. Them-polar fuzzy (mF) sets can efficiently handle such multi-faceted complications with T-norm based weighted aggregation techniques. The Aczel–Alsina T-norms offer comparatively flexible and accurate aggregation than the other well-known T-norm families. Consequently, this work introduced novelmF Aczel–Alsina aggregation operators (AOs), including weighted averaging (mFAAWA,mFAAOWA,mFAAHWA) and weighted geometric (mFAAWG,mFAAOWG,mFAAHWG) AOs. The fundamental properties, including boundedness, idempotency, monotonicity, and commutativity are investigated. Based on the proposed AOs, a decision-making algorithm is developed and implemented to solve two detailed multi-polar site selection problems (for desalination plant and for wind-power plant). Finally, a comparison withmF Dombi andmF Yager AOs reveals that different T-norm based AOs may yeild different solutions for the same problem.
Multi-wavelength interference phase imaging for automatic breast cancer detection and delineation using diffuse reflection imaging
Authors: Mahmoud Alaaeldin , El-Sharkawy Yasser H.
Published: January 2024

Millions of women globally are impacted by the major health problem of breast cancer (BC). Early detection of BC is critical for successful treatment and improved survival rates. In this study, we provide a progressive approach for BC detection using multi-wavelength interference (MWI) phase imaging based on diffuse reflection hyperspectral (HS) imaging. The proposed findings are based on the measurement of the interference pattern between the blue (446.6 nm) and red (632 nm) wavelengths. We consider implementing a comprehensive image processing and categorization method based on the use of Fast Fourier (FF) transform analysis pertaining to a change in the refractive index between tumor and normal tissue. We observed that cancer growth affects tissue organization dramatically, as seen by persistently increased refractive index variance in tumors compared normal areas. Both malignant and normal tissue had different depth data collected from it that was analyzed. To enhance the categorization of ex-vivo BC tissue, we developed and validated a training classifier algorithm specifically designed for categorizing HS cube data. Following the application of signal normalization with the FF transform algorithm, our methodology achieved a high level of performance with a specificity (Spec) of 94% and a sensitivity (Sen) of 90.9% for the 632 nm acquired image categorization, based on preliminary findings from breast specimens under investigation. Notably, we successfully leveraged unstained tissue samples to create 3D phase-resolved images that effectively highlight the distinctions in diffuse reflectance features between cancerous and healthy tissue. Preliminary data revealed that our imaging method might be able to assist specialists in safely excising malignant areas and assessing the tumor bed following resection automatically at different depths. This preliminary investigation might result in an effective "in-vivo" disease description utilizing optical technology using a typical RGB camera with wavelength-specific operation with our quantitative phase MWI imaging methodology.
Automated quantity take-off in a Norwegian road project
Authors: Fürstenberg David , Hjelseth Eilif , Klakegg Ole Jonny , Lohne Jardar , Lædre Ola
Published: January 2024

Automated quantity take-off from digital models in road projects has many benefits. In real project settings, however, it seems rarely to take place. This paper investigates automated quantity take-off in a real-life road project and the experiences from this automation. A literature and a document study were performed. 48 domain models serialized in IFC 2 × 3 were then analyzed before 10 project members were interviewed. The quantity take-off was automated to harvest classified quantities to a specification of work. The automated quantity take-off was reproducible at revisions for 40% of the cost items. However, the transferability of the procedures to other use cases than the specification of work is questionable because of the applied cost breakdown structure. The findings suggest three practical improvements for automated quantity take-off in road projects. The three include (1) using unambiguous classes assembled in an ontology, (2) avoiding hard coding of cost breakdown structures in authoring tools, and (3) implementing the Level of Information Need (LOIN) to improve reusability across project phases and use cases. The quantity take-off and experiences are assessed from the designer's perspective. The client’s and contractor’s perspectives were out of this paper’s scope.