bluuebunny/crossref_metadata_2025 huggingface dataset:
Speed of sound for understanding metals in extreme environments
Authors: Rasmussen Elizabeth G. , Wilthan Boris
Published: October 2024

Knowing material behavior is crucial for successful design, especially given the growing number of next-generation energy, defense, and manufacturing systems operating in extreme environments. Specific applications for materials in extreme environments include fusion energy, semiconductor manufacturing, metal additive manufacturing, and aerospace. With increased applications, awareness of foundational science for materials in extreme environments is imperative. The speed of sound provides insights into phase boundaries, like shock-induced melting. Thermodynamic integration of the speed of sound enables the deduction of other desirable properties that are difficult to measure accurately, like density, heat capacity, and expansivity. Metrology advancements enable the speed of sound to be measured at extreme conditions up to 15 000 K and 600 GPa. This comprehensive review presents state-of-the-art sound speed metrology while contextualizing it through a historical lens. Detailed discussions on new standards and metrology best practices, including uncertainty reporting, are included. Data availability for condensed matter speed of sound is presented, highlighting significant gaps in the literature. A theoretical section covers empirically based theoretical models like equations of state and CALPHAD models, the growing practice of using molecular dynamics and density functional theory simulations to fill gaps in measured data, and the use of artificial intelligence and machine learning prediction tools. Concluding, we review how a lack of measurement methods leads to gaps in data availability, which leads to data-driven theoretical models having higher uncertainty, thus limiting confidence in optimizing designs via numerical simulation for critical emerging technologies in extreme environments.
Recent trends in neuromorphic systems for non-von Neumann in materia computing and cognitive functionalities
Authors: Mondal Indrajit , Attri Rohit , Rao Tejaswini S. , Yadav Bhupesh , Kulkarni Giridhar U.
Published: October 2024

In the era of artificial intelligence and smart automated systems, the quest for efficient data processing has driven exploration into neuromorphic systems, aiming to replicate brain functionality and complex cognitive actions. This review assesses, based on recent literature, the challenges and progress in developing basic neuromorphic systems, focusing on “material-neuron” concepts, that integrate structural similarities, analog memory, retention, and Hebbian learning of the brain, contrasting with conventional von Neumann architecture and spiking circuits. We categorize these devices into filamentary and non-filamentary types, highlighting their ability to mimic synaptic plasticity through external stimuli manipulation. Additionally, we emphasize the importance of heterogeneous neural content to support conductance linearity, plasticity, and volatility, enabling effective processing and storage of various types of information. Our comprehensive approach categorizes fundamentally different devices under a generalized pattern dictated by the driving parameters, namely, the pulse number, amplitude, duration, interval, as well as the current compliance employed to contain the conducting pathways. We also discuss the importance of hybridization protocols in fabricating neuromorphic systems making use of existing complementary metal oxide semiconductor technologies being practiced in the silicon foundries, which perhaps ensures a smooth translation and user interfacing of these new generation devices. The review concludes by outlining insights into developing cognitive systems, current challenges, and future directions in realizing deployable neuromorphic systems in the field of artificial intelligence.
Listen Carefully
Authors: Bruun Ellen Foyn
Published: October 2024

Voice and sounding is an integrated element in dramatherapy, as in acting and life in general. This article reflects on voicework that focuses on the intimate relationship between breathing, sounding and an embodied sense of self. The notion of listen carefully emphasises the receptive aspect of arts practice and of introversion as a foundation for authentic and healthy expression. The article addresses ‘the presence of absence’ and our ability to listen with awareness to what is implicit but not yet made conscious. It was inspired by feminist philosopher Adriana Cavarero, who proposes a philosophy of voice that challenges logo-centric Western philosophical thinking. Her work underpins the relationship between voice and identity. The discussion draws from experience of three different approaches that integrate vocal somatic exploration and a holistic approach to arts, health and life. These are the legacy of Roy Hart and Alfred Wolfsohn, Movement with touch and sound (Sesame), and Fitzmaurice Voicework®. This article addresses a broad professional community interested in the field of voice in drama and theatre practice for educational and therapeutic purposes.
Roundabout and the Big Lottery: A Four Year Dramatherapy Project for Older Adults
Authors: Cedar Lynn , Crockford Susan , Elias Judy , Jackson Jane
Published: October 2024

In recent years there has been growing awareness of the needs of the ageing population in the UK. Dramatherapy is being increasingly used as a creative means of engaging with and supporting older adults, who often experience increased physical frailty, sensory impairment and/or dementia. This article explores a project that took place over a period of four years offering group dramatherapy in different London boroughs. The article covers the aims, setting up and delivery of the project and evaluation methods. Vignettes and case studies highlight specific interventions and responses, and along with outcomes, show the overall benefit of the project to the clients and organisations involved.
Mechanical properties and corrosion behavior of SiC reinforced high entropy alloy (Ni-Co-Fe-Ti) matrix composites produced by microwave and conventional sintering techniques
Authors: Pritima D , Ravichandran M , Veerappan G , Mohanavel V
Published: October 2024

The aim of this work is to synthesize SiC reinforced Ni-Co-Fe-Ti composite using powder metallurgy (PM) method. Two sintering methods, conventional sintering (CS) using a tubular furnace and microwave sintering (MWS), are employed to synthesize three different weight percentages of SiC (3 wt%, 6 wt%, and 9 wt%) within a Ni-Co-Fe-Ti matrix. The densification behavior of synthesized Ni-Co-Fe-Ti-SiC composites are studied using sinterability function. The highest sinterability of 0.89 was achieved for Ni-Co-Fe-Ti-0 wt.wt% SiC alloy. The densification rate was found to be higher in MW sintered composites compared to those sintered conventionally. 3.5 wt% NaCl solution was considered for corrosion examination and it was determined that Ni-Co-Fe-Ti- 9 wt% SiC MW sintered composite exhibit highest corrosion resistance. Ni-Co-Fe-Ti-9 wt% SiC MW sintered composite exhibits higher compressive strength of 1050 MPa than conventional sintered Ni-Co-Fe-Ti-9 wt% SiC (625 MPa). Ni-Co-Fe-Ti-6 wt% SiC MW sintered composite possess highest hardness of 58 HRC among other prepared composites. Interestingly, decreasing trend in hardness was observed for further inclusion of SiC with Ni-Co-Ti-Fe matrix. Scanning electron microscopy (SEM) and microstructural characterization technique shows the formation of pores in the conventional sintered composites. But, there is no formation of pores in the MW sintered composite of all the composition. Tribological studies were conducted using pin on disc method. Worn surface morphology was analyzed and it shows that severe pullout was observed in the worn surface of conventional sintered Ni-Co-Fe-Ti- 6 wt%SiC.The best optimum set of parameters (Sliding Speed 1146 rpm, SiC inclusion 6 wt%, Applied Load 20 N) were found out using Taguchi method.
Perceptual Knowledge and the ‘Activity’ of Belief
Authors: Roessler Johannes
Published: October 2024

In this chapter I discuss a challenge to the influential view that believing something belongs to the ‘active side’ of the human mind insofar as it implicates capacities for ‘rational agency’ or ‘rational self-determination’. Advocates of the Activity thesis (as I call it) set great store by our practice of holding each other accountable for what we believe. My question is whether they have distorted that practice by ignoring the role knowledge can play in providing credentials for belief. I articulate the challenge and then consider various lines of response to it. I conclude by suggesting that there may be no single illuminating distinction to be drawn between activity and passivity in the mind (but rather a number of sundry distinctions).
Contemporary Politics and Classical Chinese Thought
Authors: Lewis Colin J , Kling Jennifer
Published: October 2024

Analytic political philosophy is thoroughly Western in its intellectual resources and outlook. There is a great need to globalize contemporary applied political philosophy. This book takes up that call and applies classical Chinese thought to a series of current sociopolitical issues, including the construction and deconstruction of political narratives; the legal standing of robots; the relationships among people, communities, and the environment; the funding (or defunding) of police; the status of private militias; and the question of justified revolution in liberal democracies, among others. Contrary to popular opinion, classical Chinese philosophy is neither so mysterious as to be impenetrable and useless to political philosophy today, nor so commonsensical as to be banal. To make progress on the thorniest sociopolitical issues facing the world, it is imperative to bring these previously underutilized and understudied resources to bear; only then might societies attain justice, peace, and flourishing equally enjoyed by all.
Faith in Fallacy
Authors: Powell James Lawrence
Published: October 2024

Faith in Fallacy: A Century of State-Sanctioned Science Denial, by James Lawrence Powell, reveals the deadly consequences of an entire nation adopting a policy of denying consensus science. During the twentieth century, state-sanctioned science denial cost the lives of at least fifty million people, as many as the great wars. In the Soviet Union under Stalin and his agent Lysenko, denial of genetics led to lethal agricultural policies, resulting in the persecution and execution of dissenting scientists and widespread famine. In Mao’s China, the wholesale adoption of Lysenkoist pseudoscience led to a famine that claimed an estimated forty-five million lives. Hitler made state policy of Nazi eugenics, a twisted theory that held that some races are superior to others. This led first to the murder of disabled persons, including children, and then to the Holocaust. “German physics” caused the exodus of many Jewish scientists, including Einstein. President Mbeki of South Africa conducted his own internet research and concluded that HIV does not cause AIDS and that folk remedies are preferable to antiretroviral drugs, costing an estimated 330,000 deaths. In this century, in Brazil and the United States, Presidents Jair Bolsonaro and Donald Trump rejected medical advice to downplay the danger of the COVID-19 virus and discourage protective measures, causing many unnecessary deaths. Today’s Republican party rejects man-made global warming, thus denying the greatest threat that humanity has ever faced. The lesson is clear: learn from this deadly history, trust scientists and act on their advice, or cripple the lives of coming generations.
Antimicrobial Shortages: A Global Issue Impacting Infectious Diseases
Authors: Bartoo Anna S , Gilmer Mary A , Tichy Eric M
Published: October 2024

Shortages of antimicrobial agents rank second among all pharmaceutical classes. These shortages are persistent and increasing. The underlying reasons for shortages include manufacturing and quality issues, market economics, and changes in demand. Antimicrobial shortages compromise patient outcomes and increase treatment costs, contribute to antibiotic resistance, and may lead to increased adverse effects.
Ten tips to manage oral anticoagulation in hemodialysis patients with atrial fibrillation
Authors: Heine Gunnar H , Schneppe Carolin , Bauersachs Rupert , Eitel Ingo , Neuen Brendon L , Ruff Christian T , Schirmer Stephan H , De Vriese An
Published: October 2024

Patients with chronic kidney disease (CKD) have a high incidence and prevalence of atrial fibrillation (AF). While general treatment strategies for AF may largely be transferred to patients with mild to moderate CKD, patients with advanced CKD—particularly hemodialysis (HD) patients—with AF pose substantial therapeutical challenges to cardiologists and nephrologists. The arguably greatest dilemma is the very limited evidence on appropriate strategies for prevention of stroke and systemic embolism in HD patients with AF, since the risk for both thromboembolic events without oral anticoagulation and severe bleeding events with oral anticoagulation are substantially increased in advanced CKD, compared with the general population. Thus, the benefit to risk ratio of either vitamin K antagonists or direct oral anticoagulants is less evident in HD than in non-CKD patients with AF.

As a multidisciplinary panel of clinicians, we here propose 10 tips that may help our colleagues to navigate between the risk of undertreatment—exposing CKD patients with AF to a high stroke risk—and overtreatment—exposing the very same patients to a prohibitively high bleeding risk. These tips include ideas on alternative risk stratification strategies and novel treatment approaches that are currently in clinical studies—such as factor XI inhibitors or left atrial appendage closure—and may become game-changers for HD patients with AF.
Breeding season temporal and spatial trends in continental-scale migration of the monarch butterfly
Authors: Fisher Kelsey E , Filandro Alina , Bradbury Steven P , Wanamaker Alan , Coates Brad
Published: October 2024

The monarch butterfly (Danaus plexippus) is a vagile species that undertakes an annual, multi-generational migration across North America. The abundance of this species at both eastern and western overwintering sites in Central Mexico and California indicates a population decline. Success of continental-scale conservation programs for a migratory species depends on providing, maintaining, and protecting habitats at appropriate temporal and spatial scales. Here, dynamics of monarch continental-scale migration and gene flow were obtained by combined stable isotope, morphological, and genetic analyses. These analyses were applied to temporal monarch samples collected from May to September during 2016–2021 at locations in Iowa, USA and spatial collections from Pennsylvania, Delaware, Iowa, Ohio, Nevada, Idaho, Hawaii, 3 Australian locations during July and August 2016, and Texas in April 2021. Evidence of seasonal multi-generational migration was obtained through δ2H analyses of spatial collections, which was corroborated by decreased wing hue (a morphological marker for non-migratory individuals). In Iowa, 10–15% of monarchs represented migrants from southern areas throughout the breeding season and 6% were migrants from the North in midsummer. Limited sequence variation detected across the mitochondrial genome impacted the capability to detect significant population genetic variation in our North American samples. However, 2 novel substitutions were identified and predicted to be fixed among Australia samples, contributing to intercontinental differentiation from counterparts in North America. Our assessment of temporal and spatial population dynamics across the North American monarch breeding range provides insight into continental-scale migration and previously undetected mitochondrial DNA variation among globally distributed populations.
Avances y retos del plurilingüismo en los poderes públicos del estado españolProgress and challenges of multilingualism in the public powers of the Spanish state
Authors: Ridao-Martín Joan
Published: October 2024

More than four decades after the promulgation of the Spanish Constitution of 1978, its provisions on linguistic matters have been defined, through a dynamic and constructive process, by the state and regional legislators, and by the jurisprudence of the Constitutional Court, to the point of allowing a significant advance of minority languages that had been neglected for decades. Over time, this dynamic, not exempt from controversy, as corresponds to an open and plural society, has revealed some imbalances due to the asymmetry of the constitutional linguistic model, for example the scarce presence and promotion of linguistic diversity at the state level.
Trade-offs between selection of crude protein and tannins in growing lambs
Authors: Terra-Braga Marina , Poli Cesar H E C , Tontini Jalise F , Ahsin Muhammad , Van Vliet Stephan , Villalba Juan J
Published: October 2024

Tannins are phenolic compounds that provide benefits to ruminants due to their protein-binding affinities and antioxidant properties. However, tannins may also have negative orosensorial and postingestive effects that decrease feed intake. This study explored how lambs trade off the ingestion of crude protein (CP) with the ingestion of potentially beneficial and toxic condensed and hydrolyzable tannins, and the ensuing impacts on diet digestibility, animal performance, and blood parameters. Thirty-two lambs were housed in individual pens for 8 wk and had access to 2 isoenergetic diets that varied in the concentration of CP (High-high in protein [HP] or Low-least preferred [LP]) and the presence of a mix of condensed and hydrolyzable tannins (4% DM). Animals were assigned to 4 treatment groups (N = 8 lambs/group) and received a simultaneous offer of: HP and LP (Control); HP and LP + tannins (HP − LP+); HP+ tannins and LP (HP + LP−); and both HP and LP with tannins (HP + LP+). All lambs preferred HP over LP and they avoided tannins in the diets (P < 0.001). Dry matter and CP intake were the lowest in HP + LP− (P < 0.0001), and DMD did not differ between Control and the other groups (P > 0.05), but it was greater for HP − LP + (P < 0.0001). CP digestibility was greater for groups without tannins in HP (P < 0.0001), but average daily gain (ADG) did not differ among treatments (P > 0.05). No differences between Control and HP + LP + were found in plasma antioxidant activity, total phenolic concentration, or haptoglobin concentration (P > 0.05). Intake of tannins was HP + LP+ > HP + LP− > HP − LP + (P < 0.0001), and fecal excretion of nitrogen (N) was HP + LP+ > HP − LP+ = HP + LP− > Control (P < 0.05). In addition, intake of tannins with both diets reduced blood urea nitrogen (BUN) concentration relative to Control (P < 0.05), thus suggesting a shift in the partitioning of N excretion from urine to feces. In summary, lambs prioritized the selection of HP over LP, regardless of the presence of a tannin extract in either or both diets. Nevertheless, lambs modulated their tannin consumption as a function of the specific diet where the tannin extract was added, with increasing levels of intake as tannins were present in just LP, then in just HP, and finally in both diets. Dietary tannins did not constrain ADG and resulted in a shift in the partitioning of N excretion from urine to feces. Such shifts have been found to result in reduced production of environmental pollutants such as ammonia, nitrous oxide, and nitrates.
The Early Provenance of Cambridge, Corpus Christi College, MS 402 (Ancrene Wisse)
Authors: Hanna Ralph
Published: October 2024

Cambridge, Corpus Christi College, MS 402 uniquely transmits the authorial revision of the central Middle English spiritual text, Ancrene Riwle/Ancrene Wisse. The first leaf includes a note of the book’s donation to the Augustinian abbey at Wigmore (Herefs) around 1300. This note investigates the donor and the circumstances that may have prompted both the book’s production and the abbey precentor’s request for its donation.
The AP2 transcription factor BARE RECEPTACLE regulates floral organogenesis via auxin pathways in woodland strawberry
Authors: Lu Rui , Hu Shaoqiang , Feng Jia , Liu Zhongchi , Kang Chunying
Published: October 2024

During flower development, various floral organs are formed to ensure fertilization and fruit set. Although the genetic networks underlying flower development are increasingly well understood, less is known about the mechanistic basis in different species. Here, we identified a mutant of woodland strawberry (Fragaria vesca), bare receptacle (bre), which produces flowers with greatly reduced carpels and other floral organs. Genetic analysis revealed that BRE encodes an APETALA2 (AP2) transcription factor. BRE was highly expressed in floral meristems and floral organ primordia. BRE could directly bind the GCC-box motif in the YUCCA (YUC) auxin biosynthesis genes FveYUC4 and FveYUC2 and promote their expression. The yuc4 mutant had fewer floral organs, and the bre yuc4 double mutant had similar numbers of petals and carpels to bre. Auxin homeostasis and distribution were severely disrupted in bre. Although auxin application or FveYUC4 overexpression did not rescue the bre phenotypes, bre was hypersensitive to treatment with the polar auxin transport inhibitor N-1-naphthylphthalamic acid (NPA). In addition, BRE was able to directly bind and regulate the expression of five other auxin pathway genes. Overall, these results demonstrate that BRE is required for floral organogenesis, particularly carpel initiation, and acts through the auxin pathway in strawberry.
Status compensation effect in grant applications: applicants of lower status create longer titles for their grant proposals in China
Authors: Meng Liang , Chen Lei , Zhang Diandian
Published: October 2024

In this study, to examine status compensation effect we explore an intriguing behavioral pattern of grant applicants. We draw from the status compensation hypothesis and examine the influence of an applicant’s status (i.e. ranking of the applicant’s affiliated institution) on the title length of the applicant’s grant proposal. In addition, we explore the moderating effects of project discipline, the applicant’s grant approval experience, and funding amount. Information of all projects funded by the Management Science Division of the National Natural Science Foundation of China (NSFC) between 2015 and 2019 were screened and analyzed with a pooled cross-section data model. Ranking of the applicant’s institution was found to negatively predict the title length of the grant proposal. This effect is more pronounced in grants in Business Administration, for applicants with more experience in grant approval, and when a project has a larger funding amount. Findings of this study illustrate the prevalent status-induced compensatory behaviors in grant applications, which contribute to research on the compensation effect and bear practical implications for the scientific community.
SimCapture app video performance assessment versus real-time instructor-based performance evaluation of undergraduates in neonatal resuscitation—an agreement study
Authors: Sinha Anish , Nimbalkar Somashekhar M , Pujara Reshma K , Patel Purvi Rachit , Shinde Mayur K , Sethi Swati , Aradhya Rashmi , Patel Dipen Vasudev
Published: October 2024

Undergraduates are trained in the basic neonatal resuscitation programme (NRP) and evaluated for skill acquisition by NRP performance evaluation test (PET). Video use improves the validity of assessment when video-information adequacy, intrusiveness to students, and educational purpose are adequately balanced. We evaluated whether there was a difference between instructor’s real-time assessment and video-based assessment done by another independent assessor using videos recorded via the SimCapture application. Undergraduates were trained in basic neonatal resuscitation and were evaluated at the end for skill acquisition by PET as a part of a randomized control trial (RCT). Video recording of the PET assessment was done with the SimCapture app. Independent assessors evaluated recorded videos to evaluate and validate real-time instructor performance evaluation time assessments. We conducted an agreement study to evaluate the difference between a real-time instructor and video assessments. We trained 143 students; 139 videos were evaluated. The Bland–Altman plot showed good agreement. For the post-test result, 66 (47.5%) passed, and 73 (52.5%) failed according to the real-time assessment, while 61 (43.8%) passed and 78 (56.1%) failed according to the video assessment. The agreement between the two assessments was 94.9%, with a kappa value of 0.898. Indicating the need for positive pressure ventilation (PPV), 138 (99.3%) did correctly in real-time assessment, while 133 (95.6%) did correctly in video assessment with agreement of 96.4% but low kappa of 0.27. We conclude that the instructors’ assessment was excellent and didn’t differ from assessments obtained from recorded videos and vice-versa.
Scientific exploration and hypotheses concerning the meridian system in traditional Chinese medicine
Authors: Qi Wenchuan , He Bin , Gu Qingxin , Li Yongming , Liang Fanrong
Published: October 2024

The meridian theory is an important component of traditional Chinese medicine, playing a crucial role in disease diagnosis, treatment, and health preservation. Serving as the media for the effects of acupuncture, moxibustion, herbal medicine, and acupressure massage, meridians exert undeniable impact on the human body. However, the essence of meridians remains a topic of debate. Recent research has primarily focused on their anatomical structures, leading to numerous hypotheses. Simultaneously, other researchers have approached this subject from an energetic perspective, discovering information interactions within the meridian system. These findings suggest that meridians possess both physical and information dimensions, indicating that a singular approach to their study is insufficient. To bridge this gap, a shift from purely structural research toward an exploration of the information aspects of meridians is necessary. By integrating this information approach with traditional meridian theory, it may be possible to develop a new, modernized meridian theory that is aligned with contemporary concepts, making it more accessible and applicable in clinical settings.
Xanthomonas citri pv. eucalyptorum strain 4866-2_S43 (formerly X. axonopodis pv. eucalyptorum): the causal agent of bacterial leaf blight on eucalypts recovered in Argentina
Authors: Traglia German Matias , Poudel Mousami , Miño Samuel , Canteros Blanca Isabel , Minsavage G. V. , Sharma Anuj , Goss Erica M. , Jones Jeffrey B. , Gochez Alberto
Published: October 2024

We report the draft genome assembly of strain 4866-2_S43 isolated from a eucalyptus lesion in Argentina and what until recently was caused by Xanthomonas citri pv. eucalyptorum (Xce). The genome size is 5 188 607 bp, with a G+C content of 64.66%. Comparative analysis reveals that the closest relative of strain 4866-2_S43 is Xce LPF 602, isolated in Brazil. Comparison of the whole genome sequences revealed an average nucleotide identity (ANI) of 99.96% between the two strains. ANIs were determined between the whole genome sequence of strain 4866-2_S43 and the genomes of all currently validated Xanthomonas spp. These results revealed that strain 4866-2_S43 shared >95% similarity with X. citri pv. citri and X. citri pv. phaseoli, and <95% with X. euvesicatoria pv. alfalfae, X. euvesicatoria pv. perforans, and X. euvesicatoria pathovars euvesicatoria and eucalyptii.
Evaluating the impact of two next generation long-lasting insecticidal nets on malaria incidence in Uganda: an interrupted time series analysis using routine health facility data
Authors: Epstein Adrienne , Gonahasa Samuel , Namuganga Jane Frances , Nassali Martha , Maiteki-Sebuguzi Catherine , Nabende Isaiah , Snyman Katherine , Nankabirwa Joaniter I , Opigo Jimmy , Donnelly Martin J , Staedke Sarah G , Kamya Moses R , Dorsey Grant
Published: October 2024

Introduction

Malaria remains a significant public health challenge globally, particularly in sub-Saharan Africa, where progress has stalled in recent years. Long-lasting insecticidal nets (LLINs) are a critical preventive tool against malaria. This study investigated the effectiveness of newer-generation LLINs following a universal coverage campaign in Uganda.

Methods

Health facility data collected 36 months prior to LLIN distribution and 24 months after LLIN distribution were utilized from 64 sites that took part in a cluster randomized trial comparing two newer-generation LLINs (pyrethroid-PBO and pyrethroid-pyriproxyfen). Using an interrupted time series approach, we compared observed malaria incidence with counterfactual scenarios if no LLINs were distributed adjusting for precipitation, vegetation, seasonality, and care-seeking behavior. Analyses were also stratified by LLIN type and study-site level estimates of transmission intensity.

Results

Overall, malaria incidence decreased from 827 cases per 1,000 person-years in the pre-distribution period to 538 per 1,000 person-years in the post-distribution period. Interrupted time series analyses estimated a 23% reduction in malaria incidence (IRR = 0.77, 95% CI 0.65-0.91) in the first 12 months following distribution relative to what would be expected had no distribution occurred, which was not sustained in the 13-24 month post-distribution period (IRR = 0.97, 95% CI 0.75-1.28). Findings were similar when stratified by LLIN type. In the first 12 months following distribution, LLIN effectiveness was greater in the high transmission sites (IRR = 0.67, 95% CI 0.54-0.86) compared to the medium (IRR = 0.74, 95% CI 0.59-0.92) and low transmission sites (IRR = 0.87, 95% CI 0.56-1.32).

Conclusion

This study demonstrated a modest reduction in malaria incidence following the distribution of newer-generation LLINs that was sustained for only 12 months, highlighting the need for improved strategies to maintain net effectiveness. Adjusting the frequency of universal coverage campaigns based on local malaria transmission intensity may enhance control efforts.
Probing the limits of cis-acting gene regulation using a model of allelic imbalance quantitative trait loci
Authors: Seoighe Cathal , Connaire Seán , Chopra Mehak
Published: October 2024

Imbalance in gene expression between alleles is a hallmark ofcis-acting expression quantitative trait loci (eQTLs) and several methods have been developed to exploit allelic imbalance to support the identification of eQTLs. Allelic imbalance is also of scientific and, potentially, clinical interest as it can erode the degree to which the effects of deleterious variants are buffered in a diploid organism and has been reported to be associated with the penetrance of pathological genomic variants. Here, we develop and apply a statistical model that is designed to evaluate whether the genotype of a locus is associated with the degree of allelic imbalance of a gene and refer to such loci as allelic imbalance quantitative trait loci (aiQTLs). An advantage of our approach is that it does not depend on link-age disequilibrium between the aiQTL and the associated gene and is, therefore, suited to the identification of eQTLs that act incisover very large distances. We applied our model to data from the GTEx consortium and examined the relationship between the distance of an eQTL from the TSS of the associated gene and the evidence that the eQTL acts incis. Previous studies have used a distance of 1Mb from the target gene as an indication that an eQTL acts incis; however, our results suggest that the majority of eQTLs at distances more than 500 kb from the TSS of the target gene are likely to act intrans(and thus to affect both gene copies). The model used here is also well suited to comparing the overall extent of allelic imbalance between samples. We show that in some tissues allelic imbalance is correlated with age; however, this correlation may be due to changes in the abundance of immune cell populations with age, as we found strong correlations between sample-level allelic imbalance and the inferred abundance of multiple immune cell types across whole blood samples.
Mechanical constraints organize 3D tissues and orchestrate muscle differentiation
Authors: Nagle Irène , van der Spek Lorijn , Gesenhues Paul , Savy Thierry , Réa Laurent , Richert Alain , Receveur Mathieu , Delort Florence , Batonnet-Pichon Sabrina , Wilhelm Claire , Luciani Nathalie , Reffay Myriam
Published: October 2024

Biological tissues achieve proper shape and ordered structures during development through responses to internal and external signals, with mechanical cues playing a crucial role. These forces guide cellular organization, leading to complex self-organizing structures that are foundational to embryonic patterns. Emerging theories and experiments suggest that “topological morphogens” drive these processes. Despite the predominance of three-dimensional (3D) structures in biology, studying 3D tissues remains challenging due to limited model systems and the complexity of modeling. Here, we address these challenges by using self-organized cellular aggregates, specifically spindle-shaped C2C12 myoblasts, subjected to controlled mechanical stretching. Our findings reveal that these cells form a multilayered, actin-oriented tissue structure, where mechanical forces drive long-range 3D organization and muscle differentiation. Notably, tissue surface emerges as a hotspot for differentiation, correlating with directional order as shown by single molecule fluorescentin situhybridization.

Significance Statement

We explore how cells work together to form complex structures, particularly in 3D, using muscle precursors cells (C2C12 myoblasts) as a model. By applying controlled stretching forces, we found that these cells self-organize into layered tissues that guide their transformation into muscle. This research highlights the critical role of physical forces in shaping tissues, suggesting that the way cells are physically arranged and stretched in three dimensions can significantly influence their behavior and function. Our findings offer new insights into how tissues develop and could have implications for tissue engineering, where creating the right 3D environment is key to successful tissue growth and repair.
Glycogen synthase kinase-3 is essential for Tregdevelopment and function
Authors: Kandasamy Matheswaran , Andrew Hana F. , Raza Iwan G. , Mitchell Robert , Borsa Mariana , Attar Moustafa , Clarke Alexander J
Published: October 2024

Tregsare critical regulators of the immune response, but the cellular signalling pathways that control their development and homeostasis remain to be determined. We found that glycogen synthase kinase-3 (GSK3), a kinase which integrates signals from AKT and mTOR, was essential for Tregdevelopment, restraining fatal autoimmunity. Loss ofGsk3led to metabolic rewiring in Tregs, with disordered nucleotide metabolism and activation of OxPhos. Acute deletion ofGsk3did not affect Tregfrequency or numbers, but induced an effector gene expression program, and led to the formation of populations with pro-inflammatory signatures. The loss ofGsk3in Tregsprofoundly enhanced anti-tumoral immune responses and suppressed tumour growth.
Finding Agreement: fMRI-hyperscanning reveals that dyads explore in mental state space to align opinions
Authors: Speer Sebastian P.H. , Sened Haran , Mwilambwe-Tshilobo Laetitia , Falk Emily B. , Tsoi Lily , Burns Shannon M. , Tamir Diana I.
Published: October 2024

Many prize synchrony as the ingredient that turns a conversation from a debate into a delightful duet. Yet, learning from other people’s diverging opinions can also foster understanding and agreement, satisfy curiosity, and spur imagination. Using fMRI hyperscanning and natural language processing we tested how two debaters navigate conflictual conversations to find agreement. Dyads (N=60) discussed pressing societal problems while being instructed to eitherpersuadetheir partner orcompromisewith each other. Our analysis uncovered three key insights: First, individuals instructed to compromise rather than persuade tended to agree more at the end of the session. Second, hyperscanning and linguistic analyses revealed that encouraging compromise resulted in increased exploration during conversations; dyads given compromise instructions traversed more diverse mental states and topics. Third, heightened exploration was linked to greater eventual agreement. Notably, the effect of the compromise instruction on agreement was entirely mediated by the degree of exploration. Together, these results suggest that trying to find agreement may be spurred by exploration, something that happens when people are motivated to compromise but not persuade.
Patient-derived glioblastoma organoids as real-time avatars for assessing responses to clinical CAR-T cell therapy
Authors: Logun Meghan , Wang Xin , Sun Yusha , Bagley Stephen J. , Li Nannan , Desai Arati , Zhang Daniel Y. , Nasrallah MacLean P. , Pai Emily Ling-Lin , Oner Bike Su , Plesa Gabriela , Siegel Donald , Binder Zev A. , Ming Guo-li , Song Hongjun , O’Rourke Donald M.
Published: October 2024

Patient-derived tumor organoids have been leveraged for disease modeling and preclinical studies, but rarely applied in real-time to aid with interpretation of patient treatment responses in clinics. We recently demonstrated early efficacy signals in a first-in-human, phase 1 study of dual-targeting chimeric antigen receptor T cells (EGFR-IL13Rα2 CAR-T cells) in patients with recurrent glioblastoma. Here we analyzed six sets of patient-derived glioblastoma organoids (GBOs) treated concurrently with the same autologous CAR-T cell products as patients in our phase 1 study. We found that CAR-T cell treatment led to target antigen reduction and cytolysis of tumor cells in GBOs, the degree of which correlated with CAR-T cell engraftment detected in patients’ cerebrospinal fluid (CSF). Furthermore, cytokine release patterns in GBOs mirrored patient CSF samples over time. Our findings highlight a unique trial design and GBOs as a valuable platform for real-time assessment of CAR-T cell bioactivity and insights into immunotherapy efficacy.
A new spatial multi-omics approach to deeply characterize human cancer tissue using a single tissue section
Authors: Adimi Yasmine , Levin Clement , Lombardi Emilia Puig , Morin Benjamin , Gervais Claire , Tolou Sandrine , Noirot-Jagu Anne-Claude , Hauret Julie , Thomas Corinne , Tchepikoff Patricia , Grigorev Fedor , Djafri Anya , Longuemaux Sandrine , Caron Anne , Naimi Souad , Cesaroni Matteo , Tartour Eric , Classe Marion , Badoual Cecile
Published: October 2024

In the ever-changing world of digital pathology, being able to extract a maximum amount of information from a patient tissue sample is of paramount importance for better diagnosis, disease characterization, and therapeutic strategies. Recent technologies such as multiplex immunofluorescence imaging and spatial transcriptomic now enable a deep analysis of protein and gene expression while retaining the spatial context of the tissue. Here, we describe an innovative approach combining a 34-protein Phenocycler panel and transcriptome analysis using Visium on a single head and neck squamous cell carcinoma section. While protein analysis reveals the complexity of the immune phenotypes involved in the disease, transcriptome analysis reveals the intricate cellular states of cancer cells that coexist within the patient’s tumor. Finally, integrating both omics modalities, we uncover unique comparison of gene and protein expression of spatially resolved cellular subspaces.
Fixation probability in a diploid sexually reproducing population
Authors: Shi Zhenyu , Marrec Loïc , Richter Xiang-Yi Li
Published: October 2024

Classical population genetics models with haploid individuals and cloning reproduction, such as the Moran process, have limited power in predicting the evolutionary fate of mutants in diploid, sexually reproducing populations. In this work, we built a new stochastic population genetics model to fill this outstanding knowledge gap. We showed that sexual reproduction tends to suppress the fixation probability of beneficial mutants than clonal reproduction, except under overdominance. This effect is particularly large in small populations with biased sex ratios. We also found that small populations are prone to the invasion of mildly detrimental alleles when the heterozygotes have a fitness advantage. Our study highlights the pressing need to extend the research of stochastic population dynamics to consider the biology of sexual reproduction, such as allelic interactions and biased sex ratio. Our model extends the frontier of population genetics research into diploid, sexually reproducing populations and sets the foundation to explore the great variety of biological factors and processes, such as sexual selection and sexual conflict, on stochastic evolutionary dynamics. Future research in this direction will help make better predictions of the evolutionary fate of mutants in relevant contexts, including the conservation of endangered species and evolutionary rescue.
Computational design and evaluation of optimal bait sets for scalable proximity proteomics
Authors: Kasmaeifar Vesal , Sedighi Saya , Gingras Anne-Claude , Campbell Kieran R.
Published: October 2024

The spatial organization of proteins in eukaryotic cells can be explored by identifying nearby proteins using proximity-dependent biotinylation approaches like BioID. BioID defines the localization of thousands of endogenous proteins in human cells when used on hundreds of bait proteins. However, this high bait number restricts the approach’s usage and gives these datasets limited scalability for context-dependent spatial profiling. To make subcellular proteome mapping across different cell types and conditions more practical and cost-effective, we developed a comprehensive benchmarking platform and multiple metrics to assess how well a given bait subset can reproduce an original BioID dataset. We also introduce GENBAIT, which uses a genetic algorithm to optimize bait subset selection, to derive bait subsets predicted to retain the structure and coverage of two large BioID datasets using less than a third of the original baits. This flexible solution is poised to improve the intelligent selection of baits for contextual studies.
Deep Learning-Based Motif Discovery in Major Histocompatibility Complex: A Primer
Authors: Alvarez Bruno , Nielsen Morten
Published: October 2024

In this work, we present a deep learning-based approach for motif discovery in the Major Histo-compatibility Complex (MHC) system, which plays a key role in the immune response. We explore the use of convolutional neural networks (CNNs) to identify peptide binding motifs for different MHC alleles. By training models on data from specific MHC Class I and II molecules, we demonstrate how 1-dimensional convolutional filters can effectively capture motifs and binding preferences. Our study introduces a method for extracting motif logos directly from the trained models, providing insights into how internal neural network representations align with known biological motifs. The results show significant alignment with experimental binding motifs, underscoring the utility of deep learning in immunological research and the potential for improving vaccine design and immunotherapy.
A unifying theoretical framework for tick-borne disease risk to explain conflicting results of exclosure experiments across scales
Authors: Freedman Ari Seth , Levin Simon A. , Felt Stephen A. , De Leo Giulio A.
Published: October 2024

Disease ecology has focused greatly on determining how changes to biodiversity may drive infectious disease risk for humans. Fencing off experimental areas (exclosures) has been a common experimental approach to assess how removing large-bodied hosts may affect disease risk, especially with tick-borne pathogens (TBPs). However, exclosure experiments have found conflicting results based on the experiment's scale, with smaller exclosures tending to increase tick densities inside the exclosure and larger exclosures tending to decrease tick densities inside. Previously, we have lacked a unifying theoretical framework able to reconcile the results of exclosure experiments across spatial scales. We present a spatially explicit model of TBP risk incorporating tick dispersal by small competent mammal hosts which can enter the exclosure and by large incompetent mammal hosts excluded from the exclosure. Our model reproduces the scale-dependence and spatial patterning observed in past exclosure experiments while elucidating their causal mechanisms. Specifically, the modeled exclosures produce high densities of infected ticks near their boundaries, with the densities decreasing towards the exclosure's center. Empirical results have found lower tick densities at the exclosure's edge than its center, a pattern we demonstrate can also be produced if we additionally allow ticks in their free-living questing stage to disperse.
Quantitative proteomic mass spectrometry of protein kinases to determine dynamic heterogeneity of the human kinome
Authors: East Michael P. , Sprung Robert W. , Okumu Denis O. , Olivares-Quintero J. Felix , Joisa Chinmaya U. , Chen Xin , Zhang Qiang , Erdmann-Gilmore Petra , Mi Yiling , Sciaky Noah , Malone James P. , Bhatia Sonam , McCabe Ian C. , Xu Yi , Sutcliffe Matthew D. , Luo Jingqin , Spears Patricia A. , Perou Charles M. , Earp H. Shelton , Carey Lisa A. , Yeh Jen Jen , Spector David L. , Gomez Shawn M. , Spanheimer Philip M. , Townsend R. Reid , Johnson Gary L.
Published: October 2024

The kinome is a dynamic system of kinases regulating signaling networks in cells and dysfunction of protein kinases contributes to many diseases. Regulation of the protein expression of kinases alters cellular responses to environmental changes and perturbations. We configured a library of 672 proteotypic peptides to quantify >300 kinases in a single LC-MS experiment using ten micrograms protein from human tissues including biopsies. This enables absolute quantitation of kinase protein abundance at attomole-femtomole expression levels, requiring no kinase enrichment and less than ten micrograms of starting protein from flash-frozen and formalin fixed paraffin embedded tissues. Breast cancer biopsies, organoids, and cell lines were analyzed using the SureQuant method, demonstrating the heterogeneity of kinase protein expression across and within breast cancer clinical subtypes. Kinome quantitation was coupled with nanoscale phosphoproteomics, providing a feasible method for novel clinical diagnosis and understanding of patient kinome responses to treatment.
H+drives ultra-fast root-to-root responses to wounding
Authors: Ducla Julie , Di Fino Luciano , Mentzelopoulou Andriani , Talide Loïc , Besten Maarten , Bernacka-Wojcik Iwona , Sjöström Theresia Arbring , Zahid Nageena , Jämtgård Sandra , Stavrinidou Eleni , Niittylä Totte , Sprakel Joris , Marhavý Peter
Published: October 2024

The plant-to-plant communication of damage is vital for plants to mount pre-emptive defensive responses in the face of threats. A variety of threats to the well-being of plants are found below ground; yet how plant roots activate inter-plant communication is largely unclear. Here we demonstrate that a wounded root rapidly releases protons (H+), that travel faster than any other “known” soluble biochemical signal due to a specialised diffusion mechanism. Within seconds after damage, cells in neighbouring unwounded roots sense the acidification and activate tissue-specific Ca2+damage signalling. In turn, this triggers a differential growth response allowing the unwounded root to avoid the site of a potential threat. Our results reveal a non-canonical rapid response mechanism for inter-plant communication based on ultrafast proton diffusion.