bluuebunny/crossref_metadata_2025 huggingface dataset:
How Male and Female Literary Authors Write About Affect Across Cultures and Over Historical Periods
Authors: Lettieri Giada , Handjaras Giacomo , Bucci Erika , Pietrini Pietro , Cecchetti Luca
Published: September 2023

A wealth of literature suggests the existence of sex differences in how emotions are experienced, recognized, expressed, and regulated. However, to what extent these differences result from the put in place of stereotypes and social rules is still a matter of debate. Literature is an essential cultural institution, a transposition of the social life of people but also of their intimate affective experiences, which can serve to address questions of psychological relevance. Here, we created a large corpus of literary fiction enriched by authors’ metadata to measure the extent to which culture influences how men and women write about emotion. Our results show that even though before the twenty-first century and across 116 countries women more than men have written about affect, starting from 2000, this difference has diminished substantially. Also, in the past, women’s narratives were more positively laden and less arousing. While the difference in arousal is ubiquitous and still present nowadays, sex differences in valence vary as a function of culture and have dissolved in recent years. Altogether, these findings suggest that historic evolution is associated with men and women writing similarly about emotions and reveal a sizable impact of culture on the affective characteristics of the lexicon.
Enhanced phenol removal by permanganate with biogas residue biochar: catalytic role of in-situ formation of manganese dioxide and activation of biochar
Authors: Li Dongyang , Xiao Yi , Xi Beidou , Gong Tiancheng , Zhang Ting , Huang Nannan , Li Wenxuan , Yang Tianxue
Published: September 2023

Increased biogas residue related to the rapid development of anaerobic fermentation has become an urgent environmental problem. The pyrolysis of biogas residue into biochar is one of the most promising treatments. In this study, biochar derived from biogas residue was prepared, and the degradation efficiency of phenol by permanganate (KMnO4) increased from 25.3% to 73.4% in 60 min in the presence of biogas residue biochar (BRB). KMnO4 reacted with BRB to produce intermediate manganese dioxide (MnO2), while BRB was activated. The specific surface area increased by 132.25%, and the oxygen-containing functional groups C=O, C−O, and COOH increased after the reaction. The generated MnO2 complexed with BRB to form MnO2@BRB. The newly formed MnO2@BRB catalyzed KMnO4 to remove phenol, which explains the high removal efficiency of phenol. A significant removal rate was also observed for antibiotics and chlorophenols, which suggested that the KMnO4/BRB system has a relatively high ability to oxidize organic pollutants. In addition, the co-existing metal ions and the natural environment had little influence on the removal efficiency of the KMnO4/BRB system. This work provides a novel technology for the resource utilization of biogas residue and improved organic pollutant removal efficiency of KMnO4 in the presence of BRB.

Graphical abstract
Participation, prediction, and publicity: avoiding the pitfalls of applying Rawlsian ethics to AI
Authors: Bay Morten
Published: September 2023

Given the popularity of John Rawls’ theory of justice as fairness as an ethical framework in the artificial intelligence (AI) field, this article examines how the theory fits with three different conceptual applications of AI technology. First, the article discusses a proposition by Ashrafian to let an AI agent perform the deliberation that produces a Rawlsian social contract governing humans. The discussion demonstrates the inviability of such an application as it contradicts foundational aspects of Rawls’ theories. An exploration of more viable applications of Rawlsian theory in the AI context follows, introducing the distinction between intrinsic and extrinsic theoretical adherence, i.e., the difference between approaches integrating Rawlsian theory in the system design and those situating AI systems in Rawls-consistent policy/legislative frameworks. The article uses emerging AI legislation in the EU and the U.S. as well as Gabriel’s argument for adopting Rawls’ publicity criterion in the AI field as examples of extrinsic adherence to Rawlsian theory. A discussion of the epistemological challenges of predictive AI systems then illustrates some implications of intrinsic adherence to Rawlsian theory. While AI systems can make short-term predictions about human behavior with intrinsic adherence to Rawls’ theory of justice as fairness, long-term, large-scale predictions results do not adhere to the theory, but instead constitute the type of utilitarianism Rawls vehemently opposed. The article concludes with an overview of the implications of these arguments for policymakers and regulators.
Determining the risk factors of under-five morbidity in Bangladesh: a Bayesian logistic regression approach
Authors: Hossain Md. Ismail , Islam Md. Raisul , Saleheen Ahmed Abdus Saleh , Rahman Azizur , Zinia Faozia Afia , Urmy Umama Akter
Published: September 2023

Purpose

Child morbidity prevents Bangladesh from reaching the target for the Sustainable Development Goals (target 3.2) despite the country’s success in reducing child mortality rates. As a result, it's crucial to consider a child's health-related issues. Therefore, this study aims to explore the prevalence and factors associated with under-five child morbidity in Bangladesh.

Methods

The Bangladesh Demographic and Health Survey, 2017–2018, a secondary cross-sectional survey data, was used in this study, which collected information using a two-stage systematic sampling design. After association test, Bayesian estimation of binary logistic regression model was used to identify the significant risk factors of morbidity among under-five children, and a trace plot was used to try to figure out the convergence of simulation.

Results

According to the prevalence analysis of this study, it can be noted that more than one-thirds of under-five children in Bangladesh suffered from at least one of the child health-related problems, and of these, the highest prevalence of child morbidity was found in the Barisal division of Bangladesh (~ 42%). According to the Bayesian logistic regression results, higher child age and maternal education are associated with a potential decrease in the risk of child morbidity in Bangladesh. Again, male children had a 7% higher risk of morbidity than female children. Another finding was that underweight children suffered 31% more fever/diarrhea/ acute respiratory infection (ARI) related problems than others.

Conclusions

According to this study’s findings, child morbidity is still a significant issue in Bangladesh. Therefore, progress on risk factors, such as maternal education, child nutrition, etc., should be the focus of policymakers' intervention.
Modelling Lymph Propulsion in a 3D Model of Murine Collecting Vessel with Three Lymphangions in Series
Authors: Adeli Koudehi Ghazal , Silvera Delgado Carlos Alejandro , Van Impe Matthias , Cornillie Pieter , Casteleyn Christophe , Vanhove Christian , Debbaut Charlotte , Segers Patrick
Published: September 2023

The lymphatic system maintains tissue homeostasis by transporting the excess fluid from the interstitium and ultimately returning it to the venous circulation against an adverse pressure gradient and gravitational force. The spontaneous contractions of lymphangions, the building blocks of collecting vessels, and the secondary lymphatic valves play key roles in lymph propulsion. The aim of this study was to investigate lymph propulsion in a series of three contracting lymphangions in a 3D reconstructed model segmented from micro-CT scans of the collecting lymphatics in the hind limb of mice. Computational Fluid Dynamics and Fluid–Structure Interaction were used to study the behavior of flow within the collecting vessel, as well as the behavior and deformations of the vessel wall and the poroelastic interstitium. The secondary valves were modelled as porous membranes with closed or open states depending on their permeability. A sensitivity study revealed that the parameters having the most impact on the total volume of lymph propelled by active contraction of the lymphangions were the elastic modulus of the interstitium and the permeability of the secondary valves during the open states.
Medical imagery in Maximus of Tyre’s Orations
Authors: Xenophontos Sophia
Published: September 2023

Imagery is an overarching feature of Maximus of Tyre’s Orations which has never been the subject of systematic investigation. This paper provides a starting point by focusing exclusively on medical imagery, one of the most pervasive and instrumental types of imagery in Maximus’ work that has gone entirely unnoticed in the literature to date. This paper shows that Maximus uses medicine (especially its scientific basis and historical development), the physician (e.g. his skill, provision and sensitivity towards the patient), the body (its physiology and workings) and notions of health and disease with considerable diversity and creativity, in ways that make his examples stand out in relation to earlier (Platonic) or contemporary applications of the medical parallel. It argues that the use of the medical imagery in the pedagogical context in which Maximus’ Orations were performed facilitated not just clarity but also concept formation and the shaping of a moral outlook as well as the familiarisation with the proper literary references and verbal and conceptual topoi for admission into the group of the educated elite. Another main thesis is that medical imagery valorises Maximus’ philosophical status and his claims to Imperial-period acculturation, thus functioning as a trademark for the rhetorical philosophy he wished to promote.
Energy landscapes and heat capacity signatures for peptides correlate with phase separation propensity
Authors: Nicy  , Collepardo-Guevara Rosana , Joseph Jerelle A. , Wales David J.
Published: September 2023

Phase separation plays an important role in the formation of membraneless compartments within the cell and intrinsically disordered proteins with low-complexity sequences can drive this compartmentalisation. Various intermolecular forces, such as aromatic–aromatic and cation–aromatic interactions, promote phase separation. However, little is known about how the ability of proteins to phase separate under physiological conditions is encoded in their energy landscapes and this is the focus of the present investigation. Our results provide a first glimpse into how the energy landscapes of minimal peptides that contain$ \pi $–$ \pi $and cation–$ \pi $interactions differ from the peptides that lack amino acids with such interactions. The peaks in the heat capacity ($ {C}_V $) as a function of temperature report on alternative low-lying conformations that differ significantly in terms of their enthalpic and entropic contributions. The$ {C}_V $analysis and subsequent quantification of frustration of the energy landscape suggest that the interactions that promote phase separation lead to features (peaks or inflection points) at low temperatures in$ {C}_V $. More features may occur for peptides containing residues with better phase separation propensity and the energy landscape is more frustrated for such peptides. Overall, this work links the features in the underlying single-molecule potential energy landscapes to their collective phase separation behaviour and identifies quantities ($ {C}_V $and frustration metric) that can be utilised in soft material design.
Political Rage and the Value of Valuing
Authors: Rapstine Mica
Published: September 2023

This paper focuses on the question of political anger's non-instrumental justification. I argue that the case for anger is strong where anger expresses a valuable form of valuing the good. It does so only when properly integrated with non-angry emotional responsiveness to the good. The account allows us to acknowledge the non-instrumentally bad side of anger while still delivering the intuitive verdict that anger is often justified. Moreover, it provides an avenue for criticizing much of the anger run amok in contemporary political life without directly engaging entrenched moral and political views.
Listen to Your Heart – Studying Heartbeat Detection and Emotional Intelligence
Authors: D’Amico Antonella , Mangiaracina Giulia
Published: September 2023

Abstract: Perception of emotions is at the basis of scientific literature about emotions and is considered a crucial emotional function in the Mayer and Salovey hierarchical model of Emotional Intelligence. The perception of bodily signals plays an important role in the perception of one’s own and others’ emotions. Thus, the first aim of this study was to verify if interoceptive ability, referred to as the ability to perceive bodily signals or autonomic self-perception, is related to individuals’ emotional abilities measured with the MSCEIT ( Mayer-Salovey-Caruso Emotional Intelligence Test, 2002 ). Results evidenced a positive relationship between total EI and experiential area scores (perceiving emotions and sensations) and interoceptive performance scores. A second aim was to investigate if the artificial augmentation of the cardiac perception improved performances in the same tasks. Results showed that the augmented perception of the heartbeat signal did not influence any performance in MSCEIT’s subtests. We concluded that there is a significant relationship between EI and interoceptive ability but that the artificial augmentation of the perception of bodily signals does not influence MSCEIT performances.
Real-world results of autologous stem cell transplantation in newly diagnosed multiple myeloma: a report from the Canadian Myeloma Research Group database
Authors: Côté Julie , LeBlanc Richard , Mian Hira , Chu Michael P. , McCurdy Arleigh , Masih-Khan Esther , Su Jiandong , Jimenez-Zepeda Victor H. , Song Kevin , Louzada Martha , White Darrell , Sebag Michael , Reiman Anthony , Stakiw Julie , Kotb Rami , Bergstrom Debra , Aslam Muhammad , Kaedbey Rayan , Venner Christopher P. , Gul Engin , Reece Donna
Published: September 2023

Autologous stem cell transplant (ASCT) remains an important option for eligible multiple myeloma (MM) patients as part of initial therapy. Using the Canadian Myeloma Research Group (CMRG) national database, we examined the details and outcomes of ASCT performed as first-line therapy in eligible Canadian MM patients between 2007 to 2021. We included 3821 patients with 72% receiving CyBorD induction and 2061 patients receiving maintenance, consisting of lenalidomide +/- steroids in 78.3%. The median PFS and OS for patients given a single ASCT were 35.4 and 126 months. Those receiving a second induction regimen had significantly inferior outcomes, although when maintenance was used, results were comparable regardless of the number of induction regimens administered (median PFS 55.3 vs 51.1 months [p = 0.11]; median OS 158.6 vs not yet reached [p = 0.13]). Consolidation patients had a longer median PFS (55.3 vs 34.4 months [p = 0.001]), but no significant gain in median OS (p = 0.065). Patients who received lenalidomide-based maintenance experienced a median PFS of 53.7 months and OS of 159 months. In the multivariable analysis, use of any type of maintenance therapy vs no maintenance was associated with a lower risk of progression (HR 0.52 (95% CI 0.47-0.57)) and death (HR 0.58 (95% CI 0.51-0.67)). This real-world study demonstrates that, overall, first-line treatment sequence in transplant-eligible patients produces a median OS of ≥10 years. It also highlights the contribution of post-ASCT maintenance, particularly lenalidomide given until progression.
Impacts of marine heatwaves on top predator distributions are variable but predictable
Authors: Welch Heather , Savoca Matthew S. , Brodie Stephanie , Jacox Michael G. , Muhling Barbara A. , Clay Thomas A. , Cimino Megan A. , Benson Scott R. , Block Barbara A. , Conners Melinda G. , Costa Daniel P. , Jordan Fredrick D. , Leising Andrew W. , Mikles Chloe S. , Palacios Daniel M. , Shaffer Scott A. , Thorne Lesley H. , Watson Jordan T. , Holser Rachel R. , Dewitt Lynn , Bograd Steven J. , Hazen Elliott L.
Published: September 2023

Marine heatwaves cause widespread environmental, biological, and socio-economic impacts, placing them at the forefront of 21st-century management challenges. However, heatwaves vary in intensity and evolution, and a paucity of information on how this variability impacts marine species limits our ability to proactively manage for these extreme events. Here, we model the effects of four recent heatwaves (2014, 2015, 2019, 2020) in the Northeastern Pacific on the distributions of 14 top predator species of ecological, cultural, and commercial importance. Predicted responses were highly variable across species and heatwaves, ranging from near total loss of habitat to a two-fold increase. Heatwaves rapidly altered political bio-geographies, with up to 10% of predicted habitat across all species shifting jurisdictions during individual heatwaves. The variability in predicted responses across species and heatwaves portends the need for novel management solutions that can rapidly respond to extreme climate events. As proof-of-concept, we developed an operational dynamic ocean management tool that predicts predator distributions and responses to extreme conditions in near real-time.
Notch and retinoic acid signals regulate macrophage formation from endocardium downstream of Nkx2-5
Authors: Liu Norika , Kawahira Naofumi , Nakashima Yasuhiro , Nakano Haruko , Iwase Akiyasu , Uchijima Yasunobu , Wang Mei , Wu Sean M. , Minamisawa Susumu , Kurihara Hiroki , Nakano Atsushi
Published: September 2023

Hematopoietic progenitors are enriched in the endocardial cushion and contribute, in a Nkx2-5-dependent manner, to tissue macrophages required for the remodeling of cardiac valves and septa. However, little is known about the molecular mechanism of endocardial-hematopoietic transition. In the current study, we identified the regulatory network of endocardial hematopoiesis. Signal network analysis from scRNA-seq datasets revealed that genes in Notch and retinoic acid (RA) signaling are significantly downregulated in Nkx2-5-null endocardial cells. In vivo and ex vivo analyses validate that the Nkx2-5-Notch axis is essential for the generation of both hemogenic and cushion endocardial cells, and the suppression of RA signaling via Dhrs3 expression plays important roles in further differentiation into macrophages. Genetic ablation study revealed that these macrophages are essential in cardiac valve remodeling. In summary, the study demonstrates that the Nkx2-5/Notch/RA signaling plays a pivotal role in macrophage differentiation from hematopoietic progenitors.
Efficient and sustainable water electrolysis achieved by excess electron reservoir enabling charge replenishment to catalysts
Authors: Lee Gyu Rac , Kim Jun , Hong Doosun , Kim Ye Ji , Jang Hanhwi , Han Hyeuk Jin , Hwang Chang-Kyu , Kim Donghun , Kim Jin Young , Jung Yeon Sik
Published: September 2023

Suppressing the oxidation of active-Ir(III) in IrOx catalysts is highly desirable to realize an efficient and durable oxygen evolution reaction in water electrolysis. Although charge replenishment from supports can be effective in preventing the oxidation of IrOx catalysts, most supports have inherently limited charge transfer capability. Here, we demonstrate that an excess electron reservoir, which is a charged oxygen species, incorporated in antimony-doped tin oxide supports can effectively control the Ir oxidation states by boosting the charge donations to IrOx catalysts. Both computational and experimental analyses reveal that the promoted charge transfer driven by excess electron reservoir is the key parameter for stabilizing the active-Ir(III) in IrOx catalysts. When used in a polymer electrolyte membrane water electrolyzer, Ir catalyst on excess electron reservoir incorporated support exhibited 75 times higher mass activity than commercial nanoparticle-based catalysts and outstanding long-term stability for 250 h with a marginal degradation under a water-splitting current of 1 A cm−2. Moreover, Ir-specific power (74.8 kW g−1) indicates its remarkable potential for realizing gigawatt-scale H2 production for the first time.
Pathological pallidal beta activity in Parkinson’s disease is sustained during sleep and associated with sleep disturbance
Authors: Yin Zixiao , Ma Ruoyu , An Qi , Xu Yichen , Gan Yifei , Zhu Guanyu , Jiang Yin , Zhang Ning , Yang Anchao , Meng Fangang , Kühn Andrea A. , Bergman Hagai , Neumann Wolf-Julian , Zhang Jianguo
Published: September 2023

Parkinson’s disease (PD) is associated with excessive beta activity in the basal ganglia. Brain sensing implants aim to leverage this biomarker for demand-dependent adaptive stimulation. Sleep disturbance is among the most common non-motor symptoms in PD, but its relationship with beta activity is unknown. To investigate the clinical potential of beta activity as a biomarker for sleep quality in PD, we recorded pallidal local field potentials during polysomnography in PD patients off dopaminergic medication and compared the results to dystonia patients. PD patients exhibited sustained and elevated beta activity across wakefulness, rapid eye movement (REM), and non-REM sleep, which was correlated with sleep disturbance. Simulation of adaptive stimulation revealed that sleep-related beta activity changes remain unaccounted for by current algorithms, with potential negative outcomes in sleep quality and overall quality of life for patients.
AhR diminishes the efficacy of chemotherapy via suppressing STING dependent type-I interferon in bladder cancer
Authors: Ma Zikun , Li Zhiyong , Mao Yize , Ye Jingwei , Liu Zefu , Wang Yuzhao , Wei Chen , Cui Jun , Liu Zhuowei , Liang Xiaoyu
Published: September 2023

The induction of type-I interferons (IFN-Is) is important for the efficacy of chemotherapy. By investigating the role of amino acids in regulation of IFN-I production under chemo-drug treatment in bladder cancer (BC) cells, we find an inherent AhR-dependent negative feedback to restrain STING signaling and IFN-I production. Mechanistically, in a ligand dependent manner, AhR bridges STING and CUL4B/RBX1 E3 ligase complex, facilitating STING degradation through ubiquitin-proteasome pathway. Inhibition of AhR increases STING levels and reduces tumor growth under cisplatin or STING agonist treatment. Endogenous AhR ligands are mainly consisted of tryptophan (Trp) metabolites; dietary Trp restriction, blocking the key Trp metabolism rate-limiting enzyme IDO1 or inhibition of cellular Trp importation also show similar effect as AhR inhibition. Clinically, BC patients with higher intratumoral expression of AhR or stronger intratumoral Trp metabolism (higher IDO1 or Kyn levels) that lead to higher AhR activation show worse response rate to neoadjuvant chemotherapy (NAC).
Inter-bacterial mutualism promoted by public goods in a system characterized by deterministic temperature variation
Authors: Zhao Yuxiang , Liu Zishu , Zhang Baofeng , Cai Jingjie , Yao Xiangwu , Zhang Meng , Deng Ye , Hu Baolan
Published: September 2023

Mutualism is commonly observed in nature but not often reported for bacterial communities. Although abiotic stress is thought to promote microbial mutualism, there is a paucity of research in this area. Here, we monitor microbial communities in a quasi-natural composting system, where temperature variation (20 °C–70 °C) is the main abiotic stress. Genomic analyses and culturing experiments provide evidence that temperature selects for slow-growing and stress-tolerant strains (i.e., Thermobifida fusca and Saccharomonospora viridis), and mutualistic interactions emerge between them and the remaining strains through the sharing of cobalamin. Comparison of 3000 bacterial pairings reveals that mutualism is common (~39.1%) and competition is rare (~13.9%) in pairs involving T. fusca and S. viridis. Overall, our work provides insights into how high temperature can favour mutualism and reduce competition at both the community and species levels.
Simulating Chern insulators on a superconducting quantum processor
Authors: Xiang Zhong-Cheng , Huang Kaixuan , Zhang Yu-Ran , Liu Tao , Shi Yun-Hao , Deng Cheng-Lin , Liu Tong , Li Hao , Liang Gui-Han , Mei Zheng-Yang , Yu Haifeng , Xue Guangming , Tian Ye , Song Xiaohui , Liu Zhi-Bo , Xu Kai , Zheng Dongning , Nori Franco , Fan Heng
Published: September 2023

The quantum Hall effect, fundamental in modern condensed matter physics, continuously inspires new theories and predicts emergent phases of matter. Here we experimentally demonstrate three types of Chern insulators with synthetic dimensions on a programable 30-qubit-ladder superconducting processor. We directly measure the band structures of the 2D Chern insulator along synthetic dimensions with various configurations of Aubry-André-Harper chains and observe dynamical localisation of edge excitations. With these two signatures of topology, our experiments implement the bulk-edge correspondence in the synthetic 2D Chern insulator. Moreover, we simulate two different bilayer Chern insulators on the ladder-type superconducting processor. With the same and opposite periodically modulated on-site potentials for two coupled chains, we simulate topologically nontrivial edge states with zero Hall conductivity and a Chern insulator with higher Chern numbers, respectively. Our work shows the potential of using superconducting qubits for investigating different intriguing topological phases of quantum matter.
Multi-trait discovery and fine-mapping of lipid loci in 125,000 individuals of African ancestry
Authors: Kamiza Abram Bunya , Touré Sounkou M. , Zhou Feng , Soremekun Opeyemi , Cissé Cheickna , Wélé Mamadou , Touré Aboubacrine M. , Nashiru Oyekanmi , Corpas Manuel , Nyirenda Moffat , Crampin Amelia , Shaffer Jeffrey , Doumbia Seydou , Zeggini Eleftheria , Morris Andrew P. , Asimit Jennifer L. , Chikowore Tinashe , Fatumo Segun
Published: September 2023

Most genome-wide association studies (GWAS) for lipid traits focus on the separate analysis of lipid traits. Moreover, there are limited GWASs evaluating the genetic variants associated with multiple lipid traits in African ancestry. To further identify and localize loci with pleiotropic effects on lipid traits, we conducted a genome-wide meta-analysis, multi-trait analysis of GWAS (MTAG), and multi-trait fine-mapping (flashfm) in 125,000 individuals of African ancestry. Our meta-analysis and MTAG identified four and 14 novel loci associated with lipid traits, respectively. flashfm yielded an 18% mean reduction in the 99% credible set size compared to single-trait fine-mapping with JAM. Moreover, we identified more genetic variants with a posterior probability of causality >0.9 with flashfm than with JAM. In conclusion, we identified additional novel loci associated with lipid traits, and flashfm reduced the 99% credible set size to identify causal genetic variants associated with multiple lipid traits in African ancestry.
The mesencephalic locomotor region recruits V2a reticulospinal neurons to drive forward locomotion in larval zebrafish
Authors: Carbo-Tano Martin , Lapoix Mathilde , Jia Xinyu , Thouvenin Olivier , Pascucci Marco , Auclair François , Quan Feng B. , Albadri Shahad , Aguda Vernie , Farouj Younes , Hillman Elizabeth M. C. , Portugues Ruben , Del Bene Filippo , Thiele Tod R. , Dubuc Réjean , Wyart Claire
Published: September 2023

The mesencephalic locomotor region (MLR) is a brain stem area whose stimulation triggers graded forward locomotion. How MLR neurons recruit downstream vsx2+ (V2a) reticulospinal neurons (RSNs) is poorly understood. Here, to overcome this challenge, we uncovered the locus of MLR in transparent larval zebrafish and show that the MLR locus is distinct from the nucleus of the medial longitudinal fasciculus. MLR stimulations reliably elicit forward locomotion of controlled duration and frequency. MLR neurons recruit V2a RSNs via projections onto somata in pontine and retropontine areas, and onto dendrites in the medulla. High-speed volumetric imaging of neuronal activity reveals that strongly MLR-coupled RSNs are active for steering or forward swimming, whereas weakly MLR-coupled medullary RSNs encode the duration and frequency of the forward component. Our study demonstrates how MLR neurons recruit specific V2a RSNs to control the kinematics of forward locomotion and suggests conservation of the motor functions of V2a RSNs across vertebrates.
Mass media impact on opinion evolution in biased digital environments: a bounded confidence model
Authors: Pansanella Valentina , Sîrbu Alina , Kertesz Janos , Rossetti Giulio
Published: September 2023

People increasingly shape their opinions by accessing and discussing content shared on social networking websites. These platforms contain a mixture of other users’ shared opinions and content from mainstream media sources. While online social networks have fostered information access and diffusion, they also represent optimal environments for the proliferation of polluted information and contents, which are argued to be among the co-causes of polarization/radicalization phenomena. Moreover, recommendation algorithms - intended to enhance platform usage - likely augment such phenomena, generating the so-calledAlgorithmic Bias. In this work, we study the effects of the combination of social influence and mass media influence on the dynamics of opinion evolution in a biased online environment, using a recent bounded confidence opinion dynamics model with algorithmic bias as a baseline and adding the possibility to interact with one or more media outlets, modeled as stubborn agents. We analyzed four different media landscapes and found that an open-minded population is more easily manipulated by external propaganda - moderate or extremist - while remaining undecided in a more balanced information environment. By reinforcing users’ biases, recommender systems appear to help avoid the complete manipulation of the population by external propaganda.
Complexity measure based on sensitivity analysis applied to an intensive care unit system
Authors: Paiva Joao R. B. , Pacheco Viviane M. G. , Barbosa Poliana S. , Almeida Fabiana R. , Wainer Gabriel A. , Gomes Flavio A. , Coimbra Antonio P. , Calixto Wesley P.
Published: September 2023

This work proposes a system complexity metric and its application to Intensive Care Unit (ICU) system. The methodology for applying said complexity metric comprises: (i) parameters sensitivity indices calculation, (ii) mapping connections dynamics between system components, and (iii) system’s complexity calculation. After simulating the ICU computer model and using the proposed methodology, we obtained results regarding: number of admissions, number of patients in the queue, length of stay, beds in use, ICU performance, and system complexity values (in regular or overloaded operation). As the number of patients in the queue increased, the ICU system complexity also increased, indicating a need for policies to promote system robustness.
SlWRKY16 and SlWRKY31 of tomato, negative regulators of plant defense, involved in susceptibility activation following root-knot nematode Meloidogyne javanica infection
Authors: Kumar Anil , Sichov Natalia , Bucki Patricia , Miyara Sigal Brown
Published: September 2023

The involvement of WRKY transcription factors in plant-nematode interactions, and in particular, how these WRKYs participate in regulating the complex morphological and physiological changes occurring after nematode infection, are the topic of active research. We characterized the functional role of the unstudied tomato WRKY genes SlWRKY16 and SlWRKY31 in regulating tomato roots’ response to infection by the root-knot nematode Meloidogyne javanica. Using promoter–GUS reporter gene fusions and qRT-PCR, we show that both SlWRKYs are predominantly expressed during the first half of the parasitic life stages, when feeding-site induction and construction occur. Expression of SlWRKY16 increased sharply 15 days after inoculation, whereas SlWRKY31 was already induced earlier, but reached its maximum expression at this time. Both genes were downregulated at the mature female stage. To determine biological function, we produced transgenic lines overexpressing SlWRKY16 and SlWRKY31 in tomato hairy roots. Overexpression of both genes resulted in enhanced M. javanica infection, reflected by increased galling occurrence and reproduction. Expression profiling of marker genes responsive to defense-associated phytohormones indicated reductions in salicylic acid defense-related PR-1 and jasmonic acid defense-related PI in inoculated roots overexpressing SlWRK16 and SlWRKY31, respectively. Our results suggest that SlWRKY16 and SlWRKY31 function as negative regulators of plant immunity induced upon nematode infection.
Glycerol biosynthetic pathway plays an essential role in proliferation and antioxidative defense in the human enteric protozoan parasite Entamoeba histolytica
Authors: Jeelani Ghulam , Balogun Emmanuel Oluwadare , Husain Afzal , Nozaki Tomoyoshi
Published: September 2023

Amebiasis is caused by the protozoan parasite Entamoeba histolytica. Treatment options other than metronidazole and its derivatives are few, and their low efficacy against asymptomatic cyst carriers, and experimental evidence of resistance in vitro justify the discovery/repurposing campaign for new drugs against amebiasis. Global metabolic responses to oxidative stress and cysteine deprivation by E. histolytica revealed glycerol metabolism may represent a rational target for drug development. In this study using 14C-labelled glucose, only 11% of the total glucose taken up by E. histolytica trophozoites is incorporated to lipids. To better understand the role of glycerol metabolism in this parasite, we focused on characterizing two important enzymes, glycerol kinase (GK) and glycerol 3-phosphate dehydrogenase (G3PDH). Recombinant GK was biochemically characterized in detail, while G3PDH was not due to failure of protein expression and purification. GK revealed novel characteristics and unprecedented kinetic properties in reverse reaction. Gene silencing revealed that GK is essential for optimum growth, whereas G3PDH is not. Gene silencing of G3PDH caused upregulated GK expression, while that of GK resulted in upregulation of antioxidant enzymes as shown by RNA-seq analysis. Although the precise molecular link between GK and the upregulation of antioxidant enzymes was not demonstrated, the observed increase in antioxidant enzyme expression upon GK gene silencing suggests a potential connection between GK and the cellular response to oxidative stress. Together, these results provide the first direct evidence of the biological importance and coordinated regulation of the glycerol metabolic pathways for proliferation and antioxidative defense in E. histolytica, justifying the exploitation of these enzymes as future drug targets.
Prepregnancy overweight and obesity and long-term risk of venous thromboembolism in women
Authors: Mahmoud Ahmad , Sandblad Katarina Glise , Lundberg Christina E. , Hellsén Gustaf , Hansson Per Olof , Adiels Martin , Rosengren Annika
Published: September 2023

Overweight and obesity rates have increased in recent decades, particularly among the younger population. The long-term consequences of obesity with respect to early venous thromboembolism (VTE) in women have not been established. The aim was to investigate the association between body mass index (BMI) in early pregnancy as a proxy for non-pregnant weight and long-term post-pregnancy risk of VTE in women. This registry-based prospective cohort study analysed data from the Swedish Medical Birth Registry, linked to the National Patient and the National Cause of Death Registries for information on post-pregnancy long-term risk of VTE. Cox proportional hazards model were used to determine the association between BMI at baseline and VTE events during follow-up starting 1 year after baseline. The mean age at registration was 27.5 (standard deviation, 4.9) years. During a median follow-up duration of 12 years (interquartile range, 6–21 years) starting 1 year after the first antenatal visit, 1765 and 2549 women had a deep vein thrombosis and/or pulmonary embolism. The risk of VTE linearly increased with increasing BMI. Compared to women with 20 ≤ BMI < 22.5 kg/m2, women with high normal weight, i.e. with a BMI of 22.5–25.0 kg/m2, had an adjusted hazard ratio (HR) of 1.30 (95% confidence interval [CI] 1.19–1.41), whereas those with a BMI of 30–35 kg/m2 and ≥ 35 kg/m2 (severe obesity) had an adjusted HR of 2.35 (95% CI 2.04–2.70) and 3.47 (95% CI 2.82–4.25, respectively. Using BMI in early pregnancy as a proxy for pre-pregnancy or non-pregnant BMI in young women, we found a significantly increased risk of post-pregnancy long-term risk of VTE even in those with high normal BMI, compared with lean women, whereas those with severe obesity had a markedly high risk.
Linking extreme seasonality and gene expression in Arctic marine protists
Authors: Wutkowska Magdalena , Vader Anna , Logares Ramiro , Pelletier Eric , Gabrielsen Tove M.
Published: September 2023

At high latitudes, strong seasonal differences in light availability affect marine organisms and regulate the timing of ecosystem processes. Marine protists are key players in Arctic aquatic ecosystems, yet little is known about their ecological roles over yearly cycles. This is especially true for the dark polar night period, which up until recently was assumed to be devoid of biological activity. A 12 million transcripts catalogue was built from 0.45 to 10 μm protist assemblages sampled over 13 months in a time series station in an Arctic fjord in Svalbard. Community gene expression was correlated with seasonality, with light as the main driving factor. Transcript diversity and evenness were higher during polar night compared to polar day. Light-dependent functions had higher relative expression during polar day, except phototransduction. 64% of the most expressed genes could not be functionally annotated, yet up to 78% were identified in Arctic samples from Tara Oceans, suggesting that Arctic marine assemblages are distinct from those from other oceans. Our study increases understanding of the links between extreme seasonality and biological processes in pico- and nanoplanktonic protists. Our results set the ground for future monitoring studies investigating the seasonal impact of climate change on the communities of microbial eukaryotes in the High Arctic.
Quantitative detection of formaldehyde using solid phase microextraction gas chromatography–mass spectrometry coupled to cysteamine scavenging
Authors: Chothia Sara Y. , Carr Matthew , Monks Paul S. , Cordell Rebecca L. , Hopkinson Richard J.
Published: September 2023

Formaldehyde (HCHO) is a toxic and carcinogenic pollutant and human metabolite that reacts with biomolecules under physiological conditions. Quantifying HCHO is essential for ongoing biological and biomedical research on HCHO; however, its reactivity, small size and volatility make this challenging. Here, we report a novel HCHO detection/quantification method that couples cysteamine-mediated HCHO scavenging with SPME GC–MS analysis. Our NMR studies confirm cysteamine as an efficient and selective HCHO scavenger that out-competes O-(2,3,4,5,6-pentafluorobenzyl)hydroxylamine, the most commonly used scavenger, and forms a stable thiazolidine amenable to GC–MS quantification. Validation of our GC–MS method using FDA and EMA guidelines revealed detection and quantification limits in the nanomolar and micromolar ranges respectively, while analysis of bacterial cell lysate confirmed its applicability in biological samples. Overall, our studies confirm that cysteamine scavenging coupled to SPME GC–MS analysis provides a sensitive and chemically robust method to quantify HCHO in biological samples.
Genomic and transcriptomic analysis of camptothecin producing novel fungal endophyte: Alternaria burnsii NCIM 1409
Authors: Natarajan Shakunthala , Pucker Boas , Srivastava Smita
Published: September 2023

Camptothecin is an important anticancer alkaloid produced by particular plant species. No suitable synthetic route has been established for camptothecin production yet, imposing a stress on plant-based production systems. Endophytes associated with these camptothecin-producing plants have been reported to also produce camptothecin and other high-value phytochemicals. A previous study identified a fungal endophyte Alternaria burnsii NCIM 1409, isolated from Nothapodytes nimmoniana, to be a sustainable producer of camptothecin. Our study provides key insights on camptothecin biosynthesis in this recently discovered endophyte. The whole genome sequence of A. burnsii NCIM 1409 was assembled and screened for biosynthetic gene clusters. Comparative studies with related fungi supported the identification of candidate genes involved in camptothecin synthesis and also helped to understand some aspects of the endophyte’s defense against the toxic effects of camptothecin. No evidence for horizontal gene transfer of the camptothecin biosynthetic genes from the host plant to the endophyte was detected suggesting an independent evolution of the camptothecin biosynthesis in this fungus.
Duality of the SVIL expression in bladder cancer and its correlation with immune infiltration
Authors: Nie Zhenyu , Guo Na , Peng Yanling , Gao Yuanhui , Cao Hui , Zhang Shufang
Published: September 2023

SVIL is a member of the villin/gelsolin superfamily and is responsible for encoding supervillin. It has been reported to be closely related to the occurrence and development of various tumors. However, the mechanism of SVIL in bladder cancer has not been reported yet. In this research, we evaluated the relationship between SVIL expression and bladder cancer in public dataset and examined the expression of SVIL in bladder cancer cell lines, tissue microarrays and patients in our cohort. Our work determined that the expression of SVIL in bladder cancer tissue was significantly lower than that in normal tissue. However, in bladder cancer tissues, the high expression of SVIL is significantly associated with poor prognosis. This kind of duality is very novel and has great research value. The expression level of SVIL can well predict the survival time of bladder cancer patients, and is an independent risk factor of bladder cancer patients. The expression of SVIL is also closely related to the immune tumor microenvironment of bladder cancer. Our research provides a basis for personalized therapeutic targets for bladder cancer.
A multi-targeted computational drug discovery approach for repurposing tetracyclines against monkeypox virus
Authors: Alandijany Thamir A. , El-Daly Mai M. , Tolah Ahmed M. , Bajrai Leena H. , Khateb Aiah M. , Kumar Geethu S. , Dubey Amit , Dwivedi Vivek Dhar , Azhar Esam I.
Published: September 2023

Monkeypox viral infection is an emerging threat and a major concern for the human population. The lack of drug molecules to treat this disease may worsen the problem. Identifying potential drug targets can significantly improve the process of developing potent drug molecules for treating monkeypox. The proteins responsible for viral replication are attractive drug targets. Identifying potential inhibitors from known drug molecules that target these proteins can be key to finding a cure for monkeypox. In this work, two viral proteins, DNA-dependent RNA polymerase (DdRp) and viral core cysteine proteinase, were considered as potential drug targets. Sixteen antibiotic drugs from the tetracycline class were screened against both viral proteins through high-throughput virtual screening. These tetracycline class of antibiotic drugs have the ability to inhibit bacterial protein synthesis, which makes these antibiotics drugs a prominent candidate for drug repurposing. Based on the screening result obtained against DdRp, top two compounds, namely Tigecycline and Eravacycline with docking scores of − 8.88 and − 7.87 kcal/mol, respectively, were selected for further analysis. Omadacycline and minocycline, with docking scores of − 10.60 and − 7.51 kcal/mol, are the top two compounds obtained after screening proteinase with the drug library. These compounds, along with reference compounds GTP for DdRp and tecovirimat for proteinase, were used to form protein–ligand complexes, followed by their evaluation through a 300 ns molecular dynamic simulation. The MM/GBSA binding free energy calculation and principal components analysis of these selected complexes were also conducted for understanding the dynamic stability and binding affinity of these compounds with respective target proteins. Overall, this study demonstrates the repurposing of tetracycline-derived drugs as a therapeutic solution for monkeypox viral infection.
Aspirin for primary prevention in patients with high cardiovascular risk: insights from CORE-Thailand registry
Authors: Wongcharoen Wanwarang , Osataphan Nichanan , Prasertwitayakij Narawudt , Suwannasom Pannipa , Suraamornkul Swangjit , Wongtheptian Wattana , Gunaparn Siriluck , Sirikul Wachiranun , Phrommintikul Arintaya
Published: September 2023

Aspirin may be considered for primary prevention in non-elderly patients with high cardiovascular risk. However, contemporary management aimed at aggressive cardiovascular risk factor control may alter benefit-risk ratio of aspirin. Therefore, we aimed to examine the effect of aspirin for primary prevention on the long-term MACEs in a large cohort registry. Cohort Of patients with high Risk for cardiovascular Events (CORE-Thailand) registry is a prospective, multicenter, observational, longitudinal study of Thai patients with high atherosclerotic risk. Patients with established atherosclerotic cardiovascular diseases were excluded. Among 4259 patients with multiple cardiovascular risk factors, 1945 (45.7%) patients used aspirin. After propensity score matching, there were 3228 patients remained in post-matching analysis. During the median follow-up period of 58.2 months, we demonstrated that aspirin use increased risk of long-term MACEs in pre-matching cohort (unadjusted HR 1.76, 95% CI 1.43–2.17, P < 0.001) and post-matching cohort (HR 1.66 (1.31–2.10), P < 0.001). In addition, patients taking aspirin had a higher risk of bleeding than non-aspirin users in pre-matching cohort (unadjusted HR 2.28, 95% CI 1.09–4.75, P = 0.028). We demonstrated that aspirin was associated with increased risk of long-term MACEs in patients with multiple cardiovascular risk factors. Due to the non-randomized design, our results should be interpreted with caution.
Whole genome sequencing resolves 10 years diagnostic odyssey in familiar myxoma
Authors: Pálla Sára , Tőke Judit , Bozsik Anikó , Butz Henriett , Papp János , Likó István , Kuroli Enikő , Bánvölgyi András , Hamar Mátyás , Bertherat Jerome , Medvecz Márta , Patócs Attila
Published: September 2023

Carney complex (CNC) is an ultrarare disorder causing cutaneous and cardiac myxomas, primary pigmented nodular adrenocortical disease, hypophyseal adenoma, and gonadal tumours. Genetic alterations are often missed under routine genetic testing. Pathogenic variants in PRKAR1A are identified in most cases, while large exonic or chromosomal deletions have only been reported in a few cases. Our aim was to identify the causal genetic alteration in our kindred with a clinical diagnosis of CNC and prove its pathogenic role by functional investigation. Targeted testing of PRKAR1A gene, whole exome and whole genome sequencing (WGS) were performed in the proband, one clinically affected and one unaffected relative. WGS identified a novel, large, 10,662 bp (10.6 kbp; LRG_514t1:c.-10403_-7 + 265del; hg19, chr17:g.66498293_66508954del) deletion in the promoter of PRKAR1A in heterozygous form in the affected family members. The exact breakpoints and the increased enzyme activity in deletion carriers compared to wild type carrier were proved. Segregation analysis and functional evaluation of PKA activity confirmed the pathogenic role of this alteration. A novel deletion upstream of the PRKAR1A gene was proved to be the cause of CNC. Our study underlines the need for WGS in molecular genetic testing of patients with monogenic disorders where conventional genetic analysis fails.