bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigating Public Sentiment on Laryngeal Cancer in 2022 Using Machine Learning
Authors: Rao Divya , Singh Rohit , Prakashini K. , Vijayananda J.
Published: April 2023

This study aims to investigate public sentiment on laryngeal cancer via tweets in 2022 using machine learning. We aimed to analyze the public sentiment about laryngeal cancer on Twitter last year. A novel dataset was created for the purpose of this study by scraping all tweets from 1st Jan 2022 that included the hashtags #throatcancer, #laryngealcancer, #supraglotticcancer, #glotticcancer, and #subglotticcancer in their text. After all tweets underwent a fourfold data cleaning process, they were analyzed using natural language processing and sentiment analysis techniques to classify tweets into positive, negative, or neutral categories and to identify common themes and topics related to laryngeal cancer. The study analyzed a corpus of 733 tweets related to laryngeal cancer. The sentiment analysis revealed that 53% of the tweets were neutral, 34% were positive, and 13% were negative. The most common themes identified in the tweets were treatment and therapy, risk factors, symptoms and diagnosis, prevention and awareness, and emotional impact. This study highlights the potential of social media platforms like Twitter as a valuable source of real-time, patient-generated data that can inform healthcare research and practice. Our findings suggest that while Twitter is a popular platform, the limited number of tweets related to laryngeal cancer indicates that a better strategy could be developed for online communication among netizens regarding the awareness of laryngeal cancer.
Intergroup Cooperation in Shotgun Hunting Among BaYaka Foragers and Yambe Farmers from the Republic of the Congo
Authors: Kandza Vidrige H. , Jang Haneul , Ntamboudila Francy Kiabiya , Lew-Levy Sheina , Boyette Adam H.
Published: April 2023

Whereas many evolutionary models emphasize within-group cooperation or between-group competition in explaining human large-scale cooperation, recent work highlights a critical role for intergroup cooperation in human adaptation. Here we investigate intergroup cooperation in the domain of shotgun hunting in northern Republic of the Congo. In the Congo Basin broadly, forest foragers maintain relationships with neighboring farmers based on systems of exchange regulated by norms and institutions such as fictive kinship. In this study, we examine how relationships between Yambe farmers and BaYaka foragers support stable intergroup cooperation in the domain of shotgun hunting. In the study village, shotgun hunting is based on a specialization-based exchange wherein Yambe farmers contribute shotguns and access to markets to buy cartridges and sell meat while BaYaka foragers contribute their specialized forest knowledge and skill. To understand how costs and benefits are distributed, we conducted structured interviews with 77 BaYaka hunters and 15 Yambe gun owners and accompanied hunters on nine hunting trips. We found that hunts are organized in a conventional manner within a fictive kinship structure, consistent with the presence of intercultural mechanisms to stabilize cooperation. However, because bushmeat demand is high, gun owners can gain significant cash profit, while compensating hunters only with cigarettes, alcohol, and a traditional hunter’s portion of meat. To level payoffs, hunters strategically hide kills or cartridges from gun owners to feed their own families. Our results illustrate how each group prioritizes different currencies (e.g., cash, meat, family, intergroup relations) and provide insights into how intergroup cooperation is stabilized in this setting. The example of this long-standing intergroup cooperative system is discussed in terms of its contemporary entwinement with logging, the bushmeat trade, and growing market intersection.
Ausubel’s meaningful learning re-visited
Authors: Bryce T. G. K. , Blown E. J.
Published: April 2023

This review provides a critique of David Ausubel’s theory of meaningful learning and the use of advance organizers in teaching. It takes into account the developments in cognition and neuroscience which have taken place in the 50 or so years since he advanced his ideas, developments which challenge our understanding of cognitive structure and the recall of prior learning. These include (i) how effective questioning to ascertain previous knowledge necessitates in-depth Socratic dialogue; (ii) how many findings in cognition and neuroscience indicate that memory may be non-representational, thereby affecting our interpretation of student recollections; (iii) the now recognised dynamism of memory; (iv) usefully regarding concepts as abilities or simulators and skills; (v) acknowledging conscious and unconscious memory and imagery; (vi) how conceptual change involves conceptual coexistence and revision; (vii) noting linguistic and neural pathways as a result of experience and neural selection; and (viii) recommending that wider concepts of scaffolding should be adopted, particularly given the increasing focus on collaborative learning in a technological world.
New Short Scale to Measure Workers’ Attitudes Toward the Implementation of Cooperative Robots in Industrial Work Settings: Instrument Development and Exploration of Attitude Structure
Authors: Leichtmann Benedikt , Hartung Johanna , Wilhelm Oliver , Nitsch Verena
Published: April 2023

The implementation of new robotic technology at workplaces is oftentimes accompanied by social and organizational change processes. A new context-specific questionnaire was developed as a diagnostic tool to measure workers’ attitudes toward mobile cooperative manufacturing robots to provide a basis for managerial decisions and interventions—the “Attitudes toward Cooperative Industrial Robots Questionnaire” (ACIR-Q). Two samples, an online sample of 355 German manufacturing workers and a field sample of 201 workers from 4 local manufacturing companies were collected. For a large item pool, exploratory and confirmatory factor analysis was used to identify the attitudinal factor structure. Data showed a combined affective-behavioral factor and two cognitive factors on task-related and social-related beliefs. Based on this, the 12-item short scale ACIR-Q was derived using ant colony optimization. As attitudes can also be interpreted as networks of evaluative responses, network analysis was used for further insights. The small-world network structure (high clustering and connectivity) allows to hold complex attitudes and centrality measures indicate the most influential evaluative responses. Additionally, we explored relationships between workers’ attitudes and interpersonal variables (perceived competence, perceived control, and general self-efficacy), as well as social/organizational variables (trust in management, support climate, job insecurity and job characteristics). Based on the results, practical implications are suggested to improve workers’ attitudes.
Severe Plastic Deformed Zones and White Etching Layers Formed During Service of Railway Wheels
Authors: Freisinger M. , Rojacz H. , Trausmuth A. , Mayrhofer P. H.
Published: April 2023

The near-surface regions of rail wheels experience a complex thermo-mechanical loading, which varies along the location of the tread and causes severe changes to the microstructure. Occasionally, brittle white etching layers (WEL) are formed, representing a high risk of wheel damage. Therefore, we studied the depth-evolution of the surface-near microstructure along different regions of the tread of a wheel being ~ 200,000 km in service. The microstructural variations point toward a higher thermal loading history in the middle of the tread and predominant mechanical loading in the neighboring regions, where a severe plastic deformed microstructure with rolling contact fatigue cracks is present. Varieties of WEL-like microstructures were investigated, the presented analysis contributes to the knowledge of their microstructural characteristics and outpoints these regions in terms of potential crack initiation sites on railway wheels.
Load-Aware Greedy Dynamic CoMP Clustering Mechanism for DPS CoMP in 5G Networks
Authors: Chantaraskul Soamsiri , Tarbut Phornthip , Nuanyai Kittipong
Published: April 2023

Cooperative communications offered by the Coordinated Multipoint (CoMP) technique have been introduced and become an important technique in the 5G mobile networks to support very high system capacity and improve the end-user service quality, especially for the cell-edge users via the dynamic coordination of transceivers at different geographical sites. One major issue driving the performance of CoMP operation is the decision on the coopering clusters or the cluster formation strategies. In this work, an approach of CoMP clustering has been studied and proposed, the so-called load-aware greedy dynamic CoMP clustering mechanism. Our proposed CoMP clustering technique is deployed on top of the actual traffic-based load-aware Dynamic Point Selection CoMP (DPS CoMP) mechanism, which is our previously proposed mechanism. The approach is aimed at maximizing spectral efficiency with appropriate cell coordination based on well-balancing cell loads within the coordinating area of the 5G networks. System performance is numerically studied and observed for the 5G Non-Orthogonal Multiple Access (NOMA) systems embedded with our proposed mechanisms for the realistic scenarios, i.e., homogeneous network and Heterogeneous Network (HetNet) cases. Numerical results illustrate the benefit brought by our approaches in comparison with others CoMP clustering techniques as well as the potential for further improvement.
Verordnung Digitaler Gesundheitsanwendungen (DiGA) an Menschen mit depressiven Erkrankungen: Ergebnisse einer qualitativen Studie
Authors: Posselt Jacqueline , Klawunn Ronny , Dierks Marie-Luise
Published: April 2023

Hintergrund und Ziel

Digitale Gesundheitsanwendungen (DiGA) gehören seit 2020 zu den Leistungen der gesetzlichen Krankenkassen. Insbesondere für Menschen mit depressiven Erkrankungen bieten DiGA eine Möglichkeit, Wartezeiten auf eine fachärztliche oder therapeutische Versorgung zu überbrücken. Derzeit ist unklar, ob und wie Hausärzt*innen (HÄ) DiGA einsetzen. Deshalb wurde untersucht, wie sich HÄ über DiGA informieren, wie sie diese beurteilen und welche Erfahrungen sie mit der Verordnung gemacht haben.

Material und Methode

In einer qualitativen Studie wurden von 01/22 bis 04/22 Interviews mit HÄ (n = 17) durchgeführt und durch eine inhaltlich strukturierenden Inhaltsanalyse ausgewertet.

Ergebnisse

Angesichts langer Wartezeiten empfinden HÄ die Vermittlung von Patient*innen mit depressiven Erkrankungen in die fachärztliche oder therapeutische Versorgung als herausfordernd. Die zeitintensive Versorgung während dieser Wartezeit stellt eine Belastung für die hausärztlichen Ressourcen dar. Digitale Interventionen werden hier bisher von den HÄ nur begrenzt eingesetzt, das eigene Wissen über bestehende Angebote ist bislang eher gering. Chancen von DiGA liegen in der Überbrückung von Wartezeiten und der zeitnahen Verfügbarkeit in unterschiedlichen Sprachen. Die Stärkung des Selbstmanagements der Erkrankten und die Erweiterung des hausärztlichen Handlungsspektrums sind weitere positive Argumente. Kritisch betrachtet werden hingegen die unklare Evidenzlage und die im Vergleich zur persönlichen Versorgung hohen Preise von DiGA. Auch sehen HÄ bei ihren eigenen Patient*innen nur ein begrenztes Interesse für DiGA und betonen, dass der Einsatz von DiGA eine zusätzliche persönliche Begleitung benötigt.

Schlussfolgerungen

Insgesamt ist die Einschätzung von DiGA durch HÄ durchaus ambivalent: Depressive Erkrankungen stellen eine hohe Arbeitsbelastung dar. Obwohl mit DiGA inzwischen eine Möglichkeit zur Unterstützung der Versorgung besteht, werden sie nur verhalten eingesetzt.
Robust fault detection and diagnosis of primary air data sensors in the presence of atmospheric turbulence
Authors: Prabhu S. , Anitha G.
Published: April 2023

This paper presents a fault detection and diagnosis (FDD) algorithm for various faults in the primary air data sensors (PADS) of an aircraft in the presence of external disturbances such as atmospheric turbulence. Rapid wind variations due to turbulence induce excessive error in the externally fitted air data probe measurements, which may lead to loss of control and misinterpretations by the flight crew. In adverse environmental conditions, the FDD of air data prefers robust and adaptive air data estimates that use an analytical redundancy approach with fewer computations. The proposed method considers the kinematics of the aircraft instead of the dynamics used in the state-of-the-art algorithms. The advantage of using kinematics is that it can reduce modeling errors significantly, avoiding high false alarm rates in the FDD process. For the estimation of stable and accurate air data under external disturbance, the inertial navigation system and global positioning system (INS/GPS) output are considered instead of actual air data probe or sensor measurements. The proposed algorithm uses estimates of air data using an exponentially weighted adaptive extended Kalman filter (EW-AEKF) to detect and diagnose PADS faults, which can perform well even in the presence of uncertain noise due to atmospheric turbulence experienced during flight. The simulation was carried out to validate the algorithm with flight data obtained from the X-Plane flight simulator under moderate atmospheric turbulence. The simulation experiments were carried out using the MATLAB programming platform. The results show that the proposed method achieves satisfactory FDD performance with lower root mean square error (RMSE) and computation time than traditional EKF-based algorithms.
Role of arousal, subjective significance and valence of affect in task-switching effectiveness
Authors: Imbir Kamil K. , Pastwa Maciej , Wielgopolan Adrianna , Modzelewska Aleksandra , Sobieszek Adam
Published: April 2023

Switching between two concurrent tasks is an important ability of the mind. In a series of two experiments, we explored the role of activation (arousal and subjective significance) and emotional valence in shaping the effectiveness of switching between two cognitive tasks: gender-marking and emotional categorisations of verbal stimuli. We expected arousal to disrupt and subjective significance to boost the effectiveness of cognitive switching. We employed a paradigm that allowed us to present emotional words and measure the reaction latencies when a task given to the participants was switched; thus, the response was more costly than when continuing to respond to the same task. The first experiment, conducted with neutral words, showed that high subjective significance reduced reaction latencies in comparison with medium subjective significance. The second experiment showed a similar pattern only for neutral stimuli in the emotional categorisation task, but not for negative and positive stimuli. We did not find a clear effect of arousal or valence. The results of our studies suggest that subjective significance is independent of arousal in enhancing the cognitive control resources.
Brazil—A New Republic of African Letters?
Authors: Can Nazir Ahmed , Bano Issaka Maïnassara
Published: April 2023

Today, it is not the former colonial metropolis (Portugal), but a former colony (Brazil) that has become the main legitimizing center of African literature in the Portuguese language. It is also in Brazil that the largest number of studies on African literature written in other languages is produced. To illustrate this state of affairs, we begin by demonstrating how the work of Alain Mabanckou has penetrated the literary market and the Brazilian academy. After contextualizing the historical institutional dependence that characterizes French-speaking African literature in relation to the “center” (Paris) and situating Mabanckou in this dynamic, we look at how his work arrived in Brazil, the growing interest that it has awakened, and the type of studies conducted there. In the last part of the article, we show that Mabanckou is not an isolated phenomenon and is part of a historical process that began more than fifty years ago: due to the flow of translations and academic studies on works from different linguistic contexts, Brazil helps to unsettle the linguistic self-centeredness that characterizes African literary studies and reduces distances between “center” and “periphery” that guide the world literary game.
Reporting of harms in clinical trials of esketamine in depression: a systematic review
Authors: Taillefer de Laportalière Tanguy , Jullien Adeline , Yrondi Antoine , Cestac Philippe , Montastruc François
Published: April 2023

While previous systematic reviews of trials evaluating conventional antidepressants highlighted inadequacies and inconsistencies in adverse event (AE) reporting, no evaluation is available on esketamine in resistant depression. The objective of this review was to assess quality of reporting AEs in all published clinical trials studying esketamine. It also aimed to compare the proportions of AEs reported in journal articles to those recorded in the ClinicalTrial.gov Registers. Clinical trials evaluating the efficacy and safety of esketamine in depression were searched using Medline and ClinicalTrials.gov. The quality of reporting harms was assessed using a 21-item checklist from the CONSORT Extension of Harms (1 point by item). The total quality score was graded into four categories: high (17–21), moderate (12–16), low (7–11) and very low (0–6). Ten clinical trials were included in the analysis. Nine trials were classified as ‘low quality’ with regard to safety, one trial was classified as ‘moderate quality’. Compared to AEs recorded in ClinicalTrials.gov, we found that 41.5% of serious AEs and 39% of non-serious AEs were not reported in the published articles. Among them, the majority were psychiatric events but also cardiovascular events and 94% concerned patients from esketamine groups. Quality of AEs reporting in published clinical trials of esketamine was poor and harms were reported less frequently in journal publications than in ClinicalTrial.gov Registers. The study suggests that an assessment of the benefits/risks balance of esketamine based on the results reported in trial publications is flawed due to the poor accuracy and completeness of harm data.
Social gaze behavior and hyperarousal in young females with fragile X syndrome: A within-person approach
Authors: Miller Jonas G. , Sharifi Roxanna , Piccirilli Aaron , Li Rihui , Lee Cindy H. , Bartholomay Kristi L. , Jordan Tracy L. , Marzelli Matthew J. , Bruno Jennifer L. , Lightbody Amy A. , Reiss Allan L.
Published: April 2023

Children with fragile X syndrome (FXS) often avoid eye contact, a behavior that is potentially related to hyperarousal. Prior studies, however, have focused on between-person associations rather than coupling of within-person changes in gaze behaviors and arousal. In addition, there is debate about whether prompts to maintain eye contact are beneficial for individuals with FXS. In a study of young females (ages 6–16), we used eye tracking to assess gaze behavior and pupil dilation during social interactions in a group with FXS (n = 32) and a developmentally similar comparison group (n = 23). Participants engaged in semi-structured conversations with a female examiner during blocks with and without verbal prompts to maintain eye contact. We identified a social–behavioral and psychophysiological profile that is specific to females with FXS; this group exhibited lower mean levels of eye contact, significantly increased mean pupil dilation during conversations that included prompts to maintain eye contact, and showed stronger positive coupling between eye contact and pupil dilation. Our findings strengthen support for the perspective that gaze aversion in FXS reflects negative reinforcement of social avoidance behavior. We also found that behavioral skills training may improve eye contact, but maintaining eye contact appears to be physiologically taxing for females with FXS.
Kreuzschmerzen
Authors: Jesse C. Marvin , Raabe Andreas , Schär Ralph T.
Published: April 2023

Zusammenfassung. Kreuzschmerzen sind die Volkskrankheit Nummer eins und führen zu einem hohen volkswirtschaftlichen Schaden. In den meisten Fällen handelt es sich hierbei um einen nichtspezifischen Kreuzschmerz, der symptomatisch behandelt werden kann und eine hohe Selbstheilungsrate aufweist. Auch bei spezifischen Ursachen für lumbale Rückenschmerzen ist in aller Regel erst bei erschöpften konservativen Therapiemassnahmen oder im Falle von neurologischen Ausfällen oder mechanischen Instabilitäten eine operative Therapie indiziert. Insbesondere bei Patienten mit Bandscheibenvorfällen, Spinalkanalstenosen und Spondylolisthesen kann eine operative Therapie nachweislich auch langfristig zu guten bis sehr guten Ergebnissen führen. Eine sorgfältige Indikationsstellung und Patientenaufklärung sowie realistische Zielsetzungen stellen dabei Grundvoraussetzung für den Therapieerfolg dar.
Lithium Isotope Constraints on Slab and Mantle Contribution to Arc Magmas
Authors: Zhang Wei , Kitagawa Hiroshi , Nakamura Eizo
Published: April 2023

Dehydration of subducting oceanic lithosphere (slab) induces Li‐isotope fractionation between the fluid and the slab, suggested by the δ7Li variation (∼10‰) in exhumed subduction complexes. Given that arc magmas represent melt of the supraslab mantle, a large δ7Li variation is anticipated for arc volcanic rocks. However, the δ7Li values in these rocks are mostly homogeneous within the range of mid‐ocean ridge basalts (+1.6 to +5.6‰). The lack of a subduction‐related δ7Li signature has been explained by (a) homogenization by mixing of different magma sources, (b) loss of Li from the slab via dehydration, or (c) homogenization by diffusive exchange of slab‐derived Li and the mantle. The Chugoku district in SW Japan is an ideal place to study the process responsible for Li‐isotope variation in arc magmas, since the Chugoku volcanic rocks show large δ7Li variation (−1.9 to +7.4‰). High δ7Li values (+6.3 to +7.4‰) are found in some high‐Sr andesites and dacites (adakites) whereas low δ7Li values (−1.0 to −0.1‰) are found in high‐Mg andesites. The parental magmas of these rocks have been sourced from subducted oceanic crust and sediments, respectively, with various extents of the interaction with wedge mantle. The limited extents of Li isotope modification are indicated by the similarity of the δ7Li values of these rocks and their supposed sources. The models for a slab dehydration and a diffusive exchange between slab‐derived melt and mantle demonstrate that the δ7Li signatures of the sources can be preserved in the adakites if they ascent rapidly in mantle.
Heat Waves: Physical Understanding and Scientific Challenges
Authors: Barriopedro D. , García‐Herrera R. , Ordóñez C. , Miralles D. G. , Salcedo‐Sanz S.
Published: April 2023

Heat waves (HWs) can cause large socioeconomic and environmental impacts. The observed increases in their frequency, intensity and duration are projected to continue with global warming. This review synthesizes the state of knowledge and scientific challenges. It discusses different aspects related to the definition, triggering mechanisms, observed changes and future projections of HWs, as well as emerging research lines on subseasonal forecasts and specific types of HWs. We also identify gaps that limit progress and delineate priorities for future research. Overall, the physical drivers of HWs are not well understood, partly due to difficulties in the quantification of their interactions and responses to climate change. Influential factors convey processes at different spatio‐temporal scales, from global warming and the large‐scale atmospheric circulation to regional and local factors in the affected area and upwind regions. Although some thermodynamic processes have been identified, there is a lack of understanding of dynamical aspects, regional forcings and feedbacks, and their future changes. This hampers the attribution of regional trends and individual events, and reduces the ability to provide accurate forecasts and regional projections. Sustained observational networks, models of diverse complexity, narrative‐based methodological approaches and artificial intelligence offer new opportunities toward process‐based understanding and interdisciplinary research.
The Origin of Seismic and Tectonic Activity Underlying the Sichuan Basin, Central China
Authors: Su Zhe , Bürgmann Roland , Wang Erchie
Published: April 2023

The Sichuan basin, located adjacent to the eastern margin of the Tibetan Plateau, serves as an ideal marker for testing the extrusion process of the plateau. The basin is seismically active, with the strongest earthquake, the 2008 Mw 7.9 Wenchuan earthquake, occurring in the Longmen Shan range along its northwestern edge. A new regional compilation of focal mechanism solutions of earthquakes in and surrounding the basin reveals that a large fraction of the events have focal depths ranging between 8 and 25 km, corresponding to the crystalline basement of the basin. Seismic deformation involves right‐lateral oblique reverse faults, mostly trending northeast–southwest, similar to the kinematics of the mainshock of the Wenchuan earthquake. Shallow earthquakes (3–8 km) suggest that some of the seismic faults rupturing the crystalline basement are growing toward the surface. To the southwest, the seismicity transitions to activity along the left‐lateral Xianshuihe–Xiaojiang fault zone. The spatial relationship between these two sets of fault zones is consistent with a model in which the Sichuan basin responds to the southeast extrusion of the Chuan‐Dian block at the southeast margin of the plateau by a counterclockwise bookshelf rotation of the crystalline basement. This deformation pattern initiated ∼4–2 Ma, as shown by the age of the Xiaojiang fault segment. The history of left‐lateral movement along the Xianshuihe‐Xiaojiang fault can be traced back to ∼12 Ma when the eastward growth of the Tibetan Plateau resulted in the shortening of both the Longmen Shan thrust belt and the sedimentary over the Sichuan basin.
Carboxypeptidase E conditional knockout mice exhibit learning and memory deficits and neurodegeneration
Authors: Fan Fang-Cheng , Du Yang , Zheng Wen-Hui , Loh Y. Peng , Cheng Yong
Published: April 2023

Carboxypeptidase E (CPE) is a multifunctional protein with many nonenzymatic functions in various systems. Previous studies using CPE knock-out mice have shown that CPE has neuroprotective effects against stress and is involved in learning and memory. However, the functions of CPE in neurons are still largely unknown. Here we used a Camk2a-Cre system to conditionally knockout CPE in neurons. The wild-type, CPEflox/−, and CPEflox/flox mice were weaned, ear-tagged, and tail clipped for genotyping at 3 weeks old, and they underwent open field, object recognition, Y-maze, and fear conditioning tests at 8 weeks old. The CPEflox/flox mice had normal body weight and glucose metabolism. The behavioral tests showed that CPEflox/flox mice had impaired learning and memory compared with wild-type and CPEflox/- mice. Surprisingly, the subiculum (Sub) region of CPEflox/flox mice was completely degenerated, unlike the CPE full knockout mice, which exhibit CA3 region neurodegeneration. In addition, doublecortin immunostaining suggested that neurogenesis in the dentate gyrus of the hippocampus was significantly reduced in CPEflox/flox mice. Interestingly, TrkB phosphorylation in the hippocampus was downregulated in CPEflox/flox mice, but brain-derived neurotrophic factor levels were not. In both the hippocampus and dorsal medial prefrontal cortex, we observed reduced MAP2 and GFAP expression in CPEflox/flox mice. Taken together, the results of this study demonstrate that specific neuronal CPE knockout leads to central nervous system dysfunction in mice, including learning and memory deficits, hippocampal Sub degeneration and impaired neurogenesis.
High glucose-induced STING activation inhibits diabetic wound healing through promoting M1 polarization of macrophages
Authors: Geng Kang , Ma Xiumei , Jiang Zongzhe , Huang Wei , Gu Junling , Wang Peng , Luo Lifang , Xu Youhua , Xu Yong
Published: April 2023

Diabetic wound (DW) is characterized by elevated pro-inflammatory cytokines and cellular dysfunction consistent with elevated reactive oxygen species (ROS) levels. Recent advances in immunology have dissected molecular pathways involved in the innate immune system where cytoplasmic DNA can trigger STING-dependent inflammatory responses and play an important role in metabolic-related diseases. We investigated whether STING regulates inflammation and cellular dysfunction in DW healing. We found that STING and M1 macrophages were increased in wound tissues from DW in patients and mice and delayed the wound closure. We also noticed that the massively released ROS in the High glucose (HG) environment activated STING signaling by inducing the escape of mtDNA to the cytoplasm, inducing macrophage polarization into a pro-inflammatory phenotype, releasing pro-inflammatory cytokines, and exacerbating endothelial cell dysfunction. In Conclusion, mtDNA-cGAS-STING pathway activation under diabetic metabolic stress is an important mechanism of DW refractory healing. While using STING gene-edited macrophages for wound treatment by cell therapy can induce the polarization of wound macrophages from pro-inflammatory M1 to anti-inflammatory M2, promote angiogenesis, and collagen deposition to accelerate DW healing. STING may be a promising therapeutic target for DW.
Bridging clinic and wildlife care with AI-powered pan-species computational pathology
Authors: AbdulJabbar Khalid , Castillo Simon P. , Hughes Katherine , Davidson Hannah , Boddy Amy M. , Abegglen Lisa M. , Minoli Lucia , Iussich Selina , Murchison Elizabeth P. , Graham Trevor A. , Spiro Simon , Maley Carlo C. , Aresu Luca , Palmieri Chiara , Yuan Yinyin
Published: April 2023

Cancers occur across species. Understanding what is consistent and varies across species can provide new insights into cancer initiation and evolution, with significant implications for animal welfare and wildlife conservation. We build a pan-species cancer digital pathology atlas (panspecies.ai) and conduct a pan-species study of computational comparative pathology using a supervised convolutional neural network algorithm trained on human samples. The artificial intelligence algorithm achieves high accuracy in measuring immune response through single-cell classification for two transmissible cancers (canine transmissible venereal tumour, 0.94; Tasmanian devil facial tumour disease, 0.88). In 18 other vertebrate species (mammalia = 11, reptilia = 4, aves = 2, and amphibia = 1), accuracy (range 0.57–0.94) is influenced by cell morphological similarity preserved across different taxonomic groups, tumour sites, and variations in the immune compartment. Furthermore, a spatial immune score based on artificial intelligence and spatial statistics is associated with prognosis in canine melanoma and prostate tumours. A metric, named morphospace overlap, is developed to guide veterinary pathologists towards rational deployment of this technology on new samples. This study provides the foundation and guidelines for transferring artificial intelligence technologies to veterinary pathology based on understanding of morphological conservation, which could vastly accelerate developments in veterinary medicine and comparative oncology.
Modulation of antibiotic effects on microbial communities by resource competition
Authors: Newton Daniel P. , Ho Po-Yi , Huang Kerwyn Casey
Published: April 2023

Antibiotic treatment significantly impacts the human gut microbiota, but quantitative understanding of how antibiotics affect community diversity is lacking. Here, we build on classical ecological models of resource competition to investigate community responses to species-specific death rates, as induced by antibiotic activity or other growth-inhibiting factors such as bacteriophages. Our analyses highlight the complex dependence of species coexistence that can arise from the interplay of resource competition and antibiotic activity, independent of other biological mechanisms. In particular, we identify resource competition structures that cause richness to depend on the order of sequential application of antibiotics (non-transitivity), and the emergence of synergistic and antagonistic effects under simultaneous application of multiple antibiotics (non-additivity). These complex behaviors can be prevalent, especially when generalist consumers are targeted. Communities can be prone to either synergism or antagonism, but typically not both, and antagonism is more common. Furthermore, we identify a striking overlap in competition structures that lead to non-transitivity during antibiotic sequences and those that lead to non-additivity during antibiotic combination. In sum, our results establish a broadly applicable framework for predicting microbial community dynamics under deleterious perturbations.
Symmetry-broken Josephson junctions and superconducting diodes in magic-angle twisted bilayer graphene
Authors: Díez-Mérida J. , Díez-Carlón A. , Yang S. Y. , Xie Y.-M. , Gao X.-J. , Senior J. , Watanabe K. , Taniguchi T. , Lu X. , Higginbotham A. P. , Law K. T. , Efetov Dmitri K.
Published: April 2023

The coexistence of gate-tunable superconducting, magnetic and topological orders in magic-angle twisted bilayer graphene provides opportunities for the creation of hybrid Josephson junctions. Here we report the fabrication of gate-defined symmetry-broken Josephson junctions in magic-angle twisted bilayer graphene, where the weak link is gate-tuned close to the correlated insulator state with a moiré filling factor of υ = −2. We observe a phase-shifted and asymmetric Fraunhofer pattern with a pronounced magnetic hysteresis. Our theoretical calculations of the junction weak link—with valley polarization and orbital magnetization—explain most of these unconventional features. The effects persist up to the critical temperature of 3.5 K, with magnetic hysteresis observed below 800 mK. We show how the combination of magnetization and its current-induced magnetization switching allows us to realise a programmable zero-field superconducting diode. Our results represent a major advance towards the creation of future superconducting quantum electronic devices.
Mini-PCDH15 gene therapy rescues hearing in a mouse model of Usher syndrome type 1F
Authors: Ivanchenko Maryna V. , Hathaway Daniel M. , Klein Alex J. , Pan Bifeng , Strelkova Olga , De-la-Torre Pedro , Wu Xudong , Peters Cole W. , Mulhall Eric M. , Booth Kevin T. , Goldstein Corey , Brower Joseph , Sotomayor Marcos , Indzhykulian Artur A. , Corey David P.
Published: April 2023

Usher syndrome type 1 F (USH1F), caused by mutations in the protocadherin-15 gene (PCDH15), is characterized by congenital deafness, lack of balance, and progressive blindness. In hair cells, the receptor cells of the inner ear, PCDH15 is a component of tip links, fine filaments which pull open mechanosensory transduction channels. A simple gene addition therapy for USH1F is challenging because the PCDH15 coding sequence is too large for adeno-associated virus (AAV) vectors. We use rational, structure-based design to engineer mini-PCDH15s in which 3–5 of the 11 extracellular cadherin repeats are deleted, but which still bind a partner protein. Some mini-PCDH15s can fit in an AAV. An AAV encoding one of these, injected into the inner ears of mouse models of USH1F, produces a mini-PCDH15 which properly forms tip links, prevents the degeneration of hair cell bundles, and rescues hearing. Mini-PCDH15s may be a useful therapy for the deafness of USH1F.
Electron-phonon coupling and spin fluctuations in the Ising superconductor NbSe2
Authors: Das S. , Paudyal H. , Margine E. R. , Agterberg D. F. , Mazin I. I.
Published: April 2023

Ising superconductivity, observed in NbSe2 and similar materials, has generated tremendous interest. Recently, attention was called to the possible role that spin fluctuations (SF) play in this phenomenon, in addition to the dominant electron–phonon coupling (EPC); the possibility of a predominantly triplet state was discussed and led to a conjecture of viable singlet–triplet Leggett oscillations. However, these hypotheses have not been put to a quantitative test. In this paper, we report first principle calculations of the EPC and also estimate coupling with SF, including full momentum dependence. We find that: (1) EPC is strongly anisotropic, largely coming from the $$K-{K}^{{\prime} }$$

K
−

K

′

scattering, and therefore excludes triplet symmetry even as an excited state; (2) superconductivity is substantially weakened by SF, but anisotropy remains as above; and, (3) we do find the possibility of a Leggett mode, not in a singlet–triplet but in an s++ – s± channel.
Long-range inhibition synchronizes and updates prefrontal task activity
Authors: Cho Kathleen K. A. , Shi Jingcheng , Phensy Aarron J. , Turner Marc L. , Sohal Vikaas S.
Published: April 2023

Changes in patterns of activity within the medial prefrontal cortex enable rodents, non-human primates and humans to update their behaviour to adapt to changes in the environment—for example, during cognitive tasks1–5. Parvalbumin-expressing inhibitory neurons in the medial prefrontal cortex are important for learning new strategies during a rule-shift task6–8, but the circuit interactions that switch prefrontal network dynamics from maintaining to updating task-related patterns of activity remain unknown. Here we describe a mechanism that links parvalbumin-expressing neurons, a new callosal inhibitory connection, and changes in task representations. Whereas nonspecifically inhibiting all callosal projections does not prevent mice from learning rule shifts or disrupt the evolution of activity patterns, selectively inhibiting only callosal projections of parvalbumin-expressing neurons impairs rule-shift learning, desynchronizes the gamma-frequency activity that is necessary for learning8 and suppresses the reorganization of prefrontal activity patterns that normally accompanies rule-shift learning. This dissociation reveals how callosal parvalbumin-expressing projections switch the operating mode of prefrontal circuits from maintenance to updating by transmitting gamma synchrony and gating the ability of other callosal inputs to maintain previously established neural representations. Thus, callosal projections originating from parvalbumin-expressing neurons represent a key circuit locus for understanding and correcting the deficits in behavioural flexibility and gamma synchrony that have been implicated in schizophrenia and related conditions9,10.
Multisensory learning binds neurons into a cross-modal memory engram
Authors: Okray Zeynep , Jacob Pedro F. , Stern Ciara , Desmond Kieran , Otto Nils , Talbot Clifford B. , Vargas-Gutierrez Paola , Waddell Scott
Published: April 2023

Associating multiple sensory cues with objects and experience is a fundamental brain process that improves object recognition and memory performance. However, neural mechanisms that bind sensory features during learning and augment memory expression are unknown. Here we demonstrate multisensory appetitive and aversive memory in Drosophila. Combining colours and odours improved memory performance, even when each sensory modality was tested alone. Temporal control of neuronal function revealed visually selective mushroom body Kenyon cells (KCs) to be required for enhancement of both visual and olfactory memory after multisensory training. Voltage imaging in head-fixed flies showed that multisensory learning binds activity between streams of modality-specific KCs so that unimodal sensory input generates a multimodal neuronal response. Binding occurs between regions of the olfactory and visual KC axons, which receive valence-relevant dopaminergic reinforcement, and is propagated downstream. Dopamine locally releases GABAergic inhibition to permit specific microcircuits within KC-spanning serotonergic neurons to function as an excitatory bridge between the previously ‘modality-selective’ KC streams. Cross-modal binding thereby expands the KCs representing the memory engram for each modality into those representing the other. This broadening of the engram improves memory performance after multisensory learning and permits a single sensory feature to retrieve the memory of the multimodal experience.
Isolating sensory artifacts in the suprathreshold TMS-EEG signal over DLPFC
Authors: Poorganji Mohsen , Zomorrodi Reza , Hawco Colin , Hill Aron T. , Hadas Itay , Zrenner Christoph , Rajji Tarek K. , Chen Robert , Voineskos Daphne , Blumberger Daniel M. , Daskalakis Zafiris J.
Published: April 2023

Combined transcranial magnetic stimulation and electroencephalography (TMS-EEG) is an effective way to evaluate neurophysiological processes at the level of the cortex. To further characterize the TMS-evoked potential (TEP) generated with TMS-EEG, beyond the motor cortex, we aimed to distinguish between cortical reactivity to TMS versus non-specific somatosensory and auditory co-activations using both single-pulse and paired-pulse protocols at suprathreshold stimulation intensities over the left dorsolateral prefrontal cortex (DLPFC). Fifteen right-handed healthy participants received six blocks of stimulation including single and paired TMS delivered as active-masked (i.e., TMS-EEG with auditory masking and foam spacing), active-unmasked (TMS-EEG without auditory masking and foam spacing) and sham (sham TMS coil). We evaluated cortical excitability following single-pulse TMS, and cortical inhibition following a paired-pulse paradigm (long-interval cortical inhibition (LICI)). Repeated measure ANOVAs revealed significant differences in mean cortical evoked activity (CEA) of active-masked, active-unmasked, and sham conditions for both the single-pulse (F(1.76, 24.63) = 21.88,p < 0.001, η2 = 0.61) and LICI (F(1.68, 23.49) = 10.09,p < 0.001, η2 = 0.42) protocols. Furthermore, global mean field amplitude (GMFA) differed significantly across the three conditions for both single-pulse (F(1.85, 25.89) = 24.68,p < 0.001, η2 = 0.64) and LICI (F(1.8, 25.16) = 14.29,p < 0.001, η2 = 0.5). Finally, only active LICI protocols but not sham stimulation ([active-masked (0.78 ± 0.16,P < 0.0001)], [active-unmasked (0.83 ± 0.25,P < 0.01)]) resulted in significant signal inhibition. While previous findings of a significant somatosensory and auditory contribution to the evoked EEG signal are replicated by our study, an artifact attenuated cortical reactivity can reliably be measured in the TMS-EEG signal with suprathreshold stimulation of DLPFC. Artifact attenuation can be accomplished using standard procedures, and even when masked, the level of cortical reactivity is still far above what is produced by sham stimulation. Our study illustrates that TMS-EEG of DLPFC remains a valid investigational tool.
Patterns of multiple brain network activation in dot perspective task
Authors: Montandon Marie-Louise , Rodriguez Cristelle , Herrmann François R. , Eytan Ariel , Pegna Alan J. , Haller Sven , Giannakopoulos Panteleimon
Published: April 2023

In this functional MRI (fMRI) study on 82 healthy adults using the dot perspective task, inconsistency of perspectives was associated with a significant increase of the mean reaction time and number of errors both in Self and Other conditions. Unlike the Arrow (non-mentalizing), the Avatar (mentalizing) paradigm was characterized by the recruitment of parts of the mentalizing and salience networks. These data provide experimental evidence supporting the fMRI distinction between mentalizing and non-mentalizing stimuli. A widespread activation of classical theory of mind (ToM) areas but also of salience network and decision making areas was observed in the Other compared to Self-conditions. Compared to Self-Consistent, Self-Inconsistent trials were related to increased activation in the lateral occipital cortex, right supramarginal and angular gyrus as well as inferior, superior and middle frontal gyri. Compared to the Other-Consistent, Other-Inconsistent trials yielded strong activation in the lateral occipital cortex, precuneus and superior parietal lobule, middle and superior precentral gyri and left frontal pole. These findings reveal that altercentric interference relies on areas involved in self-other distinction, self-updating and central executive functions. In contrast, egocentric interference needs the activation of the mirror neuron system and deductive reasoning, much less related to pure ToM abilities.
Achieving effective interlayer bonding of PLA parts during the material extrusion process with enhanced mechanical properties
Authors: Kumar M. Saravana , Farooq Muhammad Umar , Ross Nimel Sworna , Yang Che-Hua , Kavimani V. , Adediran Adeolu A.
Published: April 2023

The additive manufacturing technique of material extrusion has challenge of excessive process defects and not achieving the desired mechanical properties. The industry is trying to develop certification to better control variations in mechanical attributes. The current study is a progress towards understanding the evolution of processing defects and the correlation of mechanical behavior with the process parameters. Modeling of the 3D printing process parameters such as layer thickness, printing speed, and printing temperature is carried out through L27 orthogonal array using Taguchi approach. In addition, CRITIC embedded WASPAS is adopted to optimize the parts' mechanical attributes and overcome the defects. Flexural and tensile poly-lactic acid specimens are printed according to ASTM standards D790 and D638, respectively, and thoroughly analyzed based on the surface morphological analysis to characterize defects. The parametric significance analysis is carried out to explore process science where the layer thickness, print speed, and temperature significantly control the quality and strength of the parts. Mathematical optimization results based on composite desirability show that layer thickness of 0.1 mm, printing speed of 60 mm/s, and printing temperature of 200 °C produce significantly desirable results. The validation experiments yielded the maximum flexural strength of 78.52 MPa, the maximum ultimate tensile strength of 45.52 MPa, and maximum impact strength of 6.21 kJ/m2. It is established that multiple fused layers restricted the propagation of cracks with minimum thickness due to enhanced diffusion between the layers.
Water discharge variations control fluvial stratigraphic architecture in the Middle Eocene Escanilla formation, Spain
Authors: Sharma Nikhil , Whittaker Alexander C. , Watkins Stephen E. , Valero Luis , Vérité Jean , Puigdefabregas Cai , Adatte Thierry , Garcés Miguel , Guillocheau François , Castelltort Sébastien
Published: April 2023

Ancient fluvial deposits typically display repetitive changes in their depositional architecture such as alternating intervals of coarse-grained highly amalgamated (HA), laterally-stacked, channel bodies, and finer-grained less amalgamated (LA), vertically-stacked, channels encased in floodplain deposits. Such patterns are usually ascribed to slower, respectively higher, rates of base level rise (accommodation). However, “upstream” factors such as water discharge and sediment flux also play a potential role in determining stratigraphic architecture, yet this possibility has never been tested despite the recent advances in the field of palaeohydraulic reconstructions from fluvial accumulations. Here, we chronicle riverbed gradient evolution within three Middle Eocene (~ 40 Ma) fluvial HA-LA sequences in the Escanilla Formation in the south-Pyrenean foreland basin. This work documents, for the first time in a fossil fluvial system, how the ancient riverbed systematically evolved from lower slopes in coarser-grained HA intervals, and higher slopes in finer-grained LA intervals, suggesting that bed slope changes were determined primarily by climate-controlled water discharge variations rather than base level changes as often hypothesized. This highlights the important connection between climate and landscape evolution and has fundamental implications for our ability to reconstruct ancient hydroclimates from the interpretation of fluvial sedimentary sequences.