bluuebunny/crossref_metadata_2025 huggingface dataset:
Low‐energy differential target multiplexed SCS derivative reduces pain and improves quality of life through 12 months in patients with chronic back and/or leg pain
Authors: Peacock Jeffery , Provenzano David , Fishman Michael , Amirdelfan Kasra , Bromberg Todd , Schmidt Todd , White Thomas , Grewal Prabhdeep , Justiz Rafael , Calodney Aaron , El‐Naggar Amr , Shah Binit , Esposito Michael , Gatzinsky Kliment , Kallewaard Jan Willem , Poree Lawrence , Cleland Andrew , Rice Calysta , Theis Erin , Noel Kate , LaRue Maddie
Published: September 2024

Introduction

Energy‐reducing spinal cord stimulation (SCS) approaches have the potential to impact patient experience with rechargeable and non‐rechargeable SCS devices through reducing device recharge time or enhancing device longevity. This prospective, multi‐center study evaluated the safety, effectiveness, and actual energy usage of differential target multiplexed (DTM) endurance therapy, a reduced energy DTM SCS derivative.

Methods

Subjects who reported an overall pain visual analog score (VAS) of ≥6/10 cm and an Oswestry Disability Index score of 21–80 out of 100 at baseline with moderate to severe chronic, intractable back and/or leg pain were eligible. Evaluation visits occurred at 1, 3, 6, and 12 months post‐device activation. The primary objective was to characterize change in overall pain intensity, as measured by VAS, from baseline to 3‐month visit.

Results

Fifty‐seven subjects enrolled at 12 US sites from November 2020 through June 2021, 35 were implanted with a rechargeable SCS device, and 27 completed the 12‐month visit. Subjects experienced a 50.4% mean reduction in overall pain from baseline at the 3‐month follow‐up that was sustained through 12 months. Additional outcomes including changes in overall, back, and leg pain intensity, quality of life, disability, therapy satisfaction, safety, and current battery usage are shown through 12‐month follow‐up.

Conclusion

The use of DTM endurance SCS therapy in this study resulted in reductions in pain relief through 12 months, demonstrating that energy‐reducing stimulation patterns can provide clinical benefit. Clinically effective, reduced energy SCS derivatives have the potential to impact patient experience through either reduced recharge requirements or increased device longevity.
10. Complex regional pain syndrome
Authors: van der Spek Daniël P. C. , Dirckx Maaike , Mangnus Thomas J. P. , Cohen Steven P. , Huygen Frank J. P. M.
Published: September 2024

Introduction

Complex regional pain syndrome (CRPS) is a clinical disorder that can develop following surgery or trauma. Based on the most prominent underlying pathophysiological mechanisms, CRPS can be classified into different subtypes, namely inflammatory, nociplastic/neuropathic, vasomotor, and motor. Depending on the subtype, personalized treatment can be applied. If conservative treatments are insufficient or ineffective, more invasive treatments may be recommended. This article provides an overview of the most recent insights into CRPS and discusses the most common invasive treatments.

Methods

The literature regarding interventional treatments for CRPS has been systematically reviewed and summarized.

Results

Bisphosphonates are effective in treating the inflammatory subtype, while ketamine can provide pain relief for the nociplastic/neuropathic subtype. Sympathetic blocks are effective in addressing vasomotor disturbances. For patients with refractory symptoms, neurostimulation is a viable option due to its multimechanistic properties for all subtypes. End‐of‐line motor disturbances may benefit from intrathecal baclofen.

Conclusions

CRPS is a debilitating condition with an unpredictable course. The effectiveness of treatment varies from patient to patient. When conservative approaches prove insufficient, gradual progression to invasive treatments based on the underlying subtype is recommended.
Recalcitrant extensive dermatophytosis in twin brothers with APECED syndrome
Authors: Najeeb Aysha , Gaurav Vishal , Dudani Pankhuri , Das Shukla , Gupta Somesh
Published: September 2024

Chronic mucocutaneous candidiasis (CMC) is characterized by recurrent infections with Candida spp., often linked to primary immunodeficiencies. We report a case of two 8‐year‐old monozygotic twin brothers presenting with extensive dermatophytosis, later diagnosed with autoimmune polyendocrinopathy, candidiasis, and ectodermal dystrophy (APECED) syndrome due to a homozygous p.M1V mutation in the AIRE gene. The twins exhibited widespread skin and nail infection, along with malabsorption, dental caries, and other autoimmune manifestations. This case highlights the novel presentation of extensive dermatophytosis in APECED, underscoring the variability in clinical expression even within a single family.
Further evidence for endozoochory in a mycoheterotrophic orchid Cyrtosia septentrionalis: seed dispersal by the masked palm civet Paguma larvata
Authors: Suetsugu K.
Published: September 2024

Cyrtosia septentrionalis, an orchid species, is notable for its sausage‐shaped red fleshy fruits, which can reach up to 10 cm in length. Previous research identified frugivorous and omnivorous birds, especially the brown‐eared bulbul Hypsipetes amaurotis (Pycnonotidae, Passeriformes), as key seed dispersers of C. septentrionalis in natural habitats. This finding challenges conventional belief that orchid seeds are primarily wind‐dispersed. Moreover, given the rarity of specialized co‐evolutionary relationships between fruits and frugivores, C. septentrionalis may also rely on mammals for seed dispersal in certain regions.

We aimed to explore the fruit consumption habits of animals other than birds. Motion sensor‐equipped cameras were used to observe interactions with the fruits of C. septentrionalis and assess the viability of seeds post‐consumption.

The observations revealed three animal species consuming the fruits, with the masked palm civet Paguma larvata (Viverridae, Carnivora) identified as a dominant consumer in the investigated population. Microscopy analysis of seeds retrieved from P. larvata faeces indicated that the seeds remained intact and viable after passing through the digestive system of this carnivorous mammal.

The above discovery suggests a potential role for carnivorous mammals in seed dispersal of C. septentrionalis, alongside birds, thus broadening our understanding of the complex seed dispersal strategies employed by orchids.
Negative plant–soil feedback influences a dominant seeded species, Western yarrow (Achillea millefolium), in grassland restoration
Authors: Casper Charles W. , DuPre Mary Ellyn , McLeod Morgan L. , Bunn Rebecca A. , Maron John L. , Ramsey Philip W. , Lekberg Ylva
Published: September 2024

Plant community ecology guides restoration of degraded lands, yet seed‐based restorations sometimes fail or result in unpredictable outcomes, necessitating a better understanding of community trajectory and stability. Western yarrow (Achillea millefolium) declined suddenly in two separate restoration projects after initial high relative abundance. To assess the potential role of soil pathogens, we surveyed plant and soil fungal communities in these restorations, and used an 8‐year‐old field experiment that crossed yarrow planted in varying densities with a fungicide treatment. Two greenhouse experiments then evaluated whether the suppressive effect in yarrow soil spread to native species used in restoration. Lower yarrow cover in a restoration project 5 years compared to 3 years after seeding coincided with higher relative abundance of fungal taxa that can cause disease, particularly Crown‐rot fungi (Paraphoma spp.). Paraphoma increased over time in experimental plots and coincided with yarrow decline. Decline onset was density‐dependent, occurring faster in plant communities where yarrow density was higher. Fungicide applications altered fungal pathogen communities and promoted yarrow cover relative to control plots. In the greenhouse, yarrow grew larger with fungicide, consistent with suppression of fungal pathogens. However, biomass of natives grown in yarrow‐conditioned soil was not affected by fungicides, suggesting pathogens did not spread. The rapid establishment and competitive nature of yarrow, followed by pathogen‐induced decline, make it an attractive early transitional “bridge species,” so long as its pathogens are species‐specific. Our results suggest negative plant‐soil feedback can drive rapid decline of individual species, and considering plant–soil feedback could improve restoration predictability.
Norms, institutions, and digital veils of uncertainty—Do network protocols need trust anyway?
Authors: Alston Eric
Published: September 2024

In large and complex human groups, social rules reduce individuals' uncertainty about their own choice set, including through these rules' simultaneous influence on the choice set of other individuals. But uncertainty varies as to the extent to which it is knowable and quantifiable ex ante. Therefore, different classes of social rules deal with the future uncertainty of individuals' conduct in structurally distinct ways, with institutions and norms being the hallmark example of this distinction. Institutions, through their costly definition and enforcement by a known organization, require specific delineation of behavior and penalties ex ante, meaning they of necessity confront “known unknowns” (risk), or the conduct of members of an organization that can be predicted ex ante. Norms, in contrast, are only effective in shaping behavior if sufficiently shared within a community, which means their application is automatic in expectation to an individual ordering their conduct considering potential norms. This makes norms apply to ex ante known and unknown situations alike, relative to the precision that the articulation of institutions requires with respect to human behavior. Although digital governance carries the benefits (and costs) of considerable institutional “completeness,” governance by protocol is nonetheless incomplete in the face of the complex set of exogenous shocks and human actions that a given digital networked organization will experience. This means digital institutions need to mimic the adaptability of institutions more generally, through the institutional mechanisms of flexibility detailed in this analysis. More generally, though, the fact that norms can serve as a complementary gap‐filler in contexts where institutions do not reach suggest that digital organization designers cannot avoid simultaneous consideration of the human community of network users that will define the norms that become crucial in periods of true uncertainty for any organization.
Effective use of skin microbiome signatures for fingerprint identification
Authors: Yılmaz Seda Salman , Kuşkucu Mert Ahmet , Çakan Hüseyin , Aygün Gökhan
Published: September 2024

Background

Recent advances have increased the importance of the human microbiome, including the skin microbiome. Despite the hand microbiome research, the factors affecting the composition of the hand microbiome and their personal characteristics are incompletely known.

Objectives

Despite changing environmental factors and personal variation, we aimed to indicate the interpersonal distinction between skin microbiota using simple and rapid molecular methods.

Methods

Over a non‐consecutive 10‐day period, samples were taken from 10 adult individuals, and ribotyping analysis of the 16S and 23S genes of S. epidermidis was performed on each skin sample. Additionally, EcoRI and HindIII enzyme reactions and variable number tandem repeat (VNTR) reactions of S. epidermidis obtained from DNA samples were performed. The skin microbiomes of individuals were evaluated along with the microbiome profiles left on the surfaces they touched.

Results

In the environmental samples taken, it has been observed that people preserve their core skin microbiota characters and carry them to their environment. It was determined that the highest similarity rate was 77.14%, and the lowest similarity rate was 31.74%.

Conclusion

Our study showed that the core skin microbiota retains its characteristics and leaves traces in environments. The fact that the personal microbiome remains unchanged despite environmental differences and has characteristic features has shown that it can be used in forensic sciences to distinguish individuals from each other. These results with simple and rapid methods further increased the importance and significance of the study. The findings indicate that personal skin microbiota can provide a significant contribution to criminal investigations by increasing accuracy and reliability, especially in forensic analyses.
Emergency Response Planning: A Framework to Assess Hydrant–Structure Access
Authors: Baik Jiwon , Murray Alan T.
Published: September 2024

Accessibility between fire hydrants and buildings is paramount in emergency response, significantly influencing the efficiency and effectiveness of firefighting operations in the event of an incident. However, assessing this relationship within a geographic information system (GIS) framework presents challenges on two fronts. Obtaining the path avoiding building and parcel obstructions to hydrants is not trivial. Further, determining the furthest extent around a building exterior from hydrants is complicated, yet it is critically important given the spatial limitations of equipment reach. To assess furthest extent, an analytical framework is introduced based on the Euclidean shortest path problem. The proposed approach offers a comprehensive, automated GIS‐based methodology tailored to evaluate the dynamic relationship between hydrants and buildings. The developed methods are able to accurately and precisely identify the furthest point around a building structure from hydrant, facilitating risk assessment as well as fire code compliance. This enables a comprehensive evaluation of potential loss and structure vulnerability at property, street, neighborhood, and regional levels.
The genetic basis of leaf hair development in upland cotton (Gossypium hirsutum)
Authors: Wang Xiaoyang , Dai Panhong , Li Hongge , Wang Jingjing , Gao Xu , Wang Zhenzhen , Peng Zhen , Tian Chunyan , Fu Guoyong , Hu Daowu , Chen Baojun , Xing Aishuang , Tian Yuan , Nazir Mian Faisal , Ma Xinli , Rong Junkang , Liu Fang , Du Xiongming , He Shoupu
Published: September 2024

Trichomes, which originate from the epidermal cell of aerial organs, provide plants with defense and secretion functions. Although numerous genes have been implicated in trichome development, the molecular mechanisms underlying trichome cell formation in plants remain incompletely understood. Here, we using genome‐wide association study (GWAS) across 1037 diverse accessions in upland cotton (Gossypium hirsutum) to identify three loci associated with leaf pubescence (hair) amount, located on chromosome A06 (LPA1), A08 (LPA2) and A11 (LPA3), respectively. GhHD1, a previously characterized candidate gene, was identified on LPA1 and encodes an HD‐Zip transcription factor. For LPA2 and LPA3, we identified two candidate genes, GhGIR1 and GhGIR2, both encoding proteins with WD40 and RING domains that act as inhibitors of leaf hair formation. Expression analysis revealed that GhHD1 was predominantly expressed in hairy accessions, whereas GhGIR1 and GhGIR2 were expressed in hairless accessions. Silencing GhHD1 or overexpressing GhGIR1 in hairy accessions induced in a hairless phenotype, whereas silencing GhGIR2 in hairless accessions resulted in a hairy phenotype. We also demonstrated that GhHD1 interact with both GhGIR1 and GhGIR2, and GhGIR1 can interact with GhGIR2. Further investigation indicated that GhHD1 functions as a transcriptional activator, binding to the promoters of the GhGIR1 and GhGIR2 to active their expression, whereas GhGIR1 and GhGIR2 can suppress the transcriptional activation of GhHD1. Our findings shed light on the intricate regulatory network involving GhHD1, GhGIR1 and GhGIR2 in the initiation and development of plant epidermal hairs in cotton.
ERFVII‐controlled hypoxia responses are in part facilitated by MEDIATOR SUBUNIT 25 in Arabidopsis thaliana
Authors: Schippers Jos H. M. , von Bongartz Kira , Laritzki Lisa , Frohn Stephanie , Frings Stephanie , Renziehausen Tilo , Augstein Frauke , Winkels Katharina , Sprangers Katrien , Sasidharan Rashmi , Vertommen Didier , Van Breusegem Frank , Hartman Sjon , Beemster Gerrit T. S. , Mhamdi Amna , van Dongen Joost T. , Schmidt‐Schippers Romy R.
Published: September 2024

Flooding impairs plant growth through oxygen deprivation, which activates plant survival and acclimation responses. Transcriptional responses to low oxygen are generally associated with the activation of group VII ETHYLENE‐RESPONSE FACTOR (ERFVII) transcription factors. However, the exact mechanisms and molecular components by which ERFVII factors initiate gene expression are not fully elucidated. Here, we show that the ERFVII factors RELATED TO APETALA 2.2 (RAP2.2) and RAP2.12 cooperate with the Mediator complex subunit AtMED25 to coordinate gene expression under hypoxia in Arabidopsis thaliana. Respective med25 knock‐out mutants display reduced low‐oxygen stress tolerance. AtMED25 physically associates with a distinct set of hypoxia core genes and its loss partially impairs transcription under hypoxia due to decreased RNA polymerase II recruitment. Association of AtMED25 with target genes requires the presence of ERFVII transcription factors. Next to ERFVII protein stabilisation, also the composition of the Mediator complex including AtMED25 is potentially affected by hypoxia stress as shown by protein‐complex pulldown assays. The dynamic response of the Mediator complex to hypoxia is furthermore supported by the fact that two subunits, AtMED8 and AtMED16, are not involved in the establishment of hypoxia tolerance, whilst both act in coordination with AtMED25 under other environmental conditions. We furthermore show that AtMED25 function under hypoxia is independent of ethylene signalling. Finally, functional conservation at the molecular level was found for the MED25‐ERFVII module between A. thaliana and the monocot species Oryza sativa, pointing to a potentially universal role of MED25 in coordinating ERFVII‐dependent transcript responses to hypoxia in plants.
Cyclic base change of cuspidal automorphic representations over function fields
Authors: Böckle Gebhard , Feng Tony , Harris Michael , Khare Chandrashekhar B. , Thorne Jack A.
Published: September 2024

Let $G$ be a split semisimple group over a global function field $K$. Given a cuspidal automorphic representation $\Pi$ of $G$ satisfying a technical hypothesis, we prove that for almost all primes $\ell$, there is a cyclic base change lifting of $\Pi$ along any $\mathbb {Z}/\ell \mathbb {Z}$-extension of $K$. Our proof does not rely on any trace formulas; instead it is based on using modularity lifting theorems, together with a Smith theory argument, to obtain base change for residual representations. As an application, we also prove that for any split semisimple group $G$ over a local function field $F$, and almost all primes $\ell$, any irreducible admissible representation of $G(F)$ admits a base change along any $\mathbb {Z}/\ell \mathbb {Z}$-extension of $F$. Finally, we characterize local base change more explicitly for a class of toral representations considered in work of Chan and Oi.
Triboinformatics Approach for Prediction of High-Stress Abrasive Wear and Coefficient of Friction in Al/TiC Nanocomposites Using Machine Learning Techniques
Authors: Golla Chitti Babu , Narasimha Rao R. , Ismail Syed
Published: September 2024

This study highlights the importance of Al–Fe–Si alloys in modern engineering for their enhanced hardness, strength, and wear resistance, improving fuel efficiency in the aerospace and automotive sectors. Data-driven analysis and machine learning methods can help understand tribological occurrences by identifying links between material characteristics and tribological behavior. The research examined TiC reinforcement in aluminum nanocomposites synthesized via ultrasonic-assisted stir casting, creating five composites with TiC weight percentages from 0% to 8%. Tests conducted using pin-on-disc equipment under various conditions, including loads of 5–15 N, sliding velocities of 0.5–1.5 m/s, sliding distances of 80–120 m, and abrasive grit sizes of 80–150 µm, revealed significant findings. The Al–6TiC nanocomposite demonstrated an 18% reduction in wear-rate at 80 µm, 28.2% at 120 µm, and 24.5% at 150 µm under a 15 N load and 120 m sliding distance compared to the pure alloy. There was also a 22% friction coefficient reduction with increased loads and grit sizes. Scanning electron microscope (SEM) analysis of the worn surfaces and abrasive papers was conducted. Wear-rate data were analyzed using six machine learning models, with the gradient boosting regressor (GBR) identified as the most accurate, achieving an R2 value of 0.95. This study emphasizes the impact of the TiC content, loading conditions, and hardness on wear and friction coefficient, and shows how machine learning techniques can predict and optimize advanced aluminum nanocomposite design for engineering applications.
Surrogate Modeling of Brain Trauma Risks Associated With Soccer Ball Headers
Authors: Perkins Richard A. , Bakhtiarydavijani Amirhamed , Sharma Gehendra , Nellippallil Anand , Hammi Youssef , Robinson Thomas , Prabhu Raj K.
Published: September 2024

This study presents a coupled mathematical surrogate modeling and finite element analysis to quantify the risk of brain injury resulting from contact between a soccer ball and a player's head. Our approach implements a previously developed and validated regulation size finite element soccer ball and a 50th percentile adult male head model to inform the surrogate models regarding the positioning of the soccer ball's impact, inbound velocity, and the role of the activation of the neck musculature. Surrogate models are developed using injury metrics such as HIC15 and BrIC, which can be correlated to clinical assessments. The surrogate models predict occipital-temporal impacts as the highest risk of injury along a perpendicular axis and highlight the risk of increased velocity and passive neck musculature. The surrogate model predicts the worst-case scenarios to produce HIC15 and BrIC values of approximately 80 and 0.65, which correlate to 4.27% of a minor head injury (AIS1) and 71% of a moderate head injury (AIS2), respectively. These models are also used to develop a graphical user interface that may be used to supplement existing clinical knowledge of soccer headings to improve the head health of athletes participating in the game of soccer.
Efficient Neural Hybrid System Learning and Interpretable Transition System Abstraction for Dynamical Systems
Authors: Yang Yejiang , Mo Zihao , Xiang Weiming
Published: September 2024

This article proposes a neural network hybrid modeling framework for dynamics learning to promote an interpretable, computationally efficient method of dynamics learning and system identification. First, a low-level model is trained to learn the system dynamics, which utilizes multiple simple neural networks to approximate the local dynamics generated from data-driven partitions. Then, based on the low-level model, a high-level model is trained to abstract the low-level neural hybrid system model into a transition system that allows computational tree logic (CTL) verification to promote model’s ability to handle human interaction and verification efficiency.
Investigating Microstructure and Wear Characteristics of Alloy Steels Used as Wear Plates in Ballast Cleaning Operation in Railways
Authors: Pandey Manas , Kumar Nikhil
Published: September 2024

Ballast cleaning machines play a pivotal role in maintaining the stability and safety of railway tracks by transferring and redistributing ballast on the tracks. However, the wear plates used in these machines are subjected to extreme conditions, making the assessment of their wear performance crucial. This study scrutinizes the wear performance of two distinct 31Ni10Cr3Mo6 based alloy steels used as wear plates in the ballast cleaning machines. The study compares the initial microstructure and wear properties of German grade steel (Plasser) wear plate with an indigenous grade steel (RDSO) used as an alternative. The results indicate that the indigenous wear plate consistently exhibits higher weight loss across various loading conditions, whereas the Plasser wear plate demonstrates superior wear resistance, particularly at higher loads. This enhanced performance is attributed to relatively larger amount of high-angle grain boundaries, small grain size, and variations in micro-alloying elements. The compositional analysis indicates low carbon content in both wear plates. The microstructural analysis shows that both samples have a single body-centered cubic crystal structure, with a randomly distributed heterogeneous ferritic and cementite phases in a lath-bainitic microstructure. This comprehensive study provides valuable insights into the wear behavior of these alloy steels, contributing to the optimization of alloying materials and desired microstructure for the wear plates in ballast cleaning machines.
Identifying kinetic models from reactor measurements
Authors: Dake Prithvi , Ilagan Maria Rikaela , Banerjee Shoili , Scott Susannah L. , Rawlings James B.
Published: September 2024

This paper investigates parameter estimation of rate constants appearing in chemical mechanisms. As most chemical mechanisms are more complex than can be supported by available laboratory measurements, model reduction is a required first step. The quasisteady-state assumption and the reaction equilibrium assumption are presented as the two main model reduction methods. Reliable quantification of the approximate confidence intervals of the estimated parameters is a second key step. A brief overview of current numerical software for this purpose is provided. Parameter estimation with a starting mechanism and typically available simulated laboratory measurements is then applied to three illustrative example systems: (i) an electrochemical oxygen reduction reaction, (ii) butene isomerization by a metathesis mechanism, and (iii) enzymatic kinetics taking place in bacterial microcompartments. The reliability of the model reduction techniques and the current computational software is assessed based on the outcomes of these three example chemistries. In all three examples, the quasisteady-state assumption was required to remove some large rate constants governing low concentration, highly reactive species that could not be measured. After the model reduction, the parameter confidence intervals were then used to determine what extra measurements were required to identify the model, or the model was reparameterized to obtain an identifiable reduced set of parameters for the given measurements.
Ti-Zr-Nb-(V) refractory alloy coatings deposited by high-power impulse magnetron sputtering: Structure, mechanical properties, oxidation resistance, and thermal stability
Authors: Fraile A. , Cavaleiro D. , Bondarev A. , Middleburgh S. C. , Lee W. E. , Fernandes F.
Published: September 2024

A series of TiZrNb(V) high entropy alloy-based metallic coatings have been deposited using high-power impulse magnetron sputtering (HiPIMS), with variable V concentrations and constant ratios among the other metals. The coatings were analyzed regarding their composition, surface and cross-sectional morphologies, microstructure, roughness, mechanical properties, oxidation resistance, and thermal stability. The structure of the deposited coatings reveals a transition from the bcc crystal structure to an amorphous phase as the V concentration increases. The addition of V also led to a decrease in roughness Ra and an improvement in adhesion, while it did not affect hardness, which remained at ∼10–11 GPa for all samples. Annealing under a protective atmosphere at 400 °C caused structural ordering, which was followed by an increase in mechanical properties. The purpose of the present paper is, therefore, to present a study on the deposition of TiZrNb coatings with increasing V concentration prepared by HiPIMS and to understand the role of V concentration on their structure, chemical composition, mechanical properties, and oxidation resistance. Comparison of the results with those achieved for a reference TiZrNb coating is presented too.
Individual variability in the use of tonal and non-tonal cues in intonation
Authors: Hu Na , Arvaniti Amalia
Published: September 2024

Greek uses H*, L + H*, and H* + L, all followed by L-L% edge tones, as nuclear pitch accents in statements. A previous analysis demonstrated that these accents are distinguished by F0 scaling and contour shape. This study expands the earlier investigation by exploring additional cues, namely, voice quality, amplitude, and duration, in distinguishing the pitch accents, and investigating individual variability in the selection of both F0 and non-F0 cues. Bayesian multivariate analysis and hierarchical clustering demonstrate that the accents are distinguished not only by F0 but also by additional cues at the group level, with individual variability in cue selection.
Toward a dynamic national transportation noise map: Modeling temporal variability of spectral traffic noise emission levels
Authors: Cook Mylan R. , Gee Kent L. , Transtrum Mark. K. , Lympany Shane V.
Published: September 2024

The National Transportation Noise Map predicts time-averaged road traffic noise across the continental United States (CONUS) based on annual average daily traffic counts. However, traffic noise can vary greatly with time. This paper outlines a method for predicting nationwide hourly varying source traffic sound emissions called the Vehicular Reduced-Order Observation-based Model (VROOM). The method incorporates three models that predict temporal variability of traffic volume, predict temporal variability of different traffic classes, and use Traffic Noise Model (TNM) 3.0 equations to give traffic noise emission levels based on vehicle numbers and class mix. Location-specific features are used to predict average class mix across CONUS. VROOM then incorporates dynamic traffic class mix data to obtain dynamic traffic class mix. TNM 3.0 equations then give estimated equivalent sound level emission spectra near roads with up to hourly resolution. Important temporal traffic noise characteristics are modeled, including diurnal traffic patterns, rush hours in urban locations, and weekly and yearly variation. Examples of the temporal variability are depicted and possible types of uncertainties are identified. Altogether, VROOM can be used to map national transportation noise with temporal and spectral variability.
Simultaneous electromechanical monitoring in engineered heart tissues using a mesoscale framework
Authors: Fullenkamp Dominic E. , Maeng Woo-Youl , Oh Seyong , Luan Haiwen , Kim Kyung Su , Chychula Ivana A. , Kim Jin-Tae , Yoo Jae-Young , Holgren Cory W. , Demonbreun Alexis R. , George Sharon , Li Binjie , Hsu Yaching , Chung Gooyoon , Yoo Jeongmin , Koo Jahyun , Park Yoonseok , Efimov Igor R. , McNally Elizabeth M. , Rogers John A.
Published: September 2024

Engineered heart tissues (EHTs) generated from human induced pluripotent stem cell–derived cardiomyocytes (hiPSC-CMs) represent powerful platforms for human cardiac research, especially in drug testing and disease modeling. Here, we report a flexible, three-dimensional electronic framework that enables real-time, spatiotemporal analysis of electrophysiologic and mechanical signals in EHTs under physiological loading conditions for dynamic, noninvasive, longer-term assessments. These electromechanically monitored EHTs support multisite measurements throughout the tissue under baseline conditions and in response to stimuli. Demonstrations include uses in tracking physiological responses to pharmacologically active agents and in capturing electrophysiological characteristics of reentrant arrhythmias. This platform facilitates precise analysis of signal location and conduction velocity in human cardiomyocyte tissues, as the basis for a broad range of advanced cardiovascular studies.
Three-dimensional valley-contrasting sound
Authors: Xue Haoran , Ge Yong , Cheng Zheyu , Guan Yi-jun , Zhu Jiaojiao , Zou Hong-yu , Yuan Shou-qi , Yang Shengyuan A. , Sun Hong-xiang , Chong Yidong , Zhang Baile
Published: September 2024

Spin and valley are two fundamental properties of electrons in crystals. The similarity between them is well understood in valley-contrasting physics established decades ago in two-dimensional (2D) materials like graphene—with broken inversion symmetry, the two valleys in graphene exhibit opposite orbital magnetic moments, similar to the spin-1/2 behaviors of electrons, and opposite Berry curvature that leads to a half topological charge. However, valley-contrasting physics has never been explored in 3D crystals. Here, we develop a 3D acoustic crystal exhibiting 3D valley-contrasting physics. Unlike spin that is fundamentally binary, valley in 3D can take six different values, each carrying a vortex in a distinct direction. The topological valley transport is generalized from the edge states of 2D materials to the surface states of 3D materials, with interesting features including robust propagation, topological refraction, and valley-cavity localization. Our results open a new route for wave manipulation in 3D space.
Crack densification in drying colloidal suspensions
Authors: Lilin Paul , Ibrahim Mario , Bischofberger Irmgard
Published: September 2024

As sessile drops of aqueous colloidal suspensions dry, a close-packed particle deposit forms that grows from the edge of the drop toward the center. To compensate for evaporation over the solid’s surface, water flows radially through the deposit, generating a negative pore pressure in the deposit associated with tensile drying stresses that induce the formation of cracks. As these stresses increase during drying, existing cracks propagate and additional cracks form, until the crack density eventually saturates. We rationalize the dynamics of crack propagation and crack densification with a local energy balance between the elastic energy released by the crack, the energetic cost of fracture, and the elastic energy released by previously formed cracks. We show that the final spacing between radial cracks is proportional to the local thickness of the deposit, while the aspect ratio of the crack segments depends on the shape of the deposit.
Positive allosteric modulation of a GPCR ternary complex
Authors: Burger Wessel A. C. , Draper-Joyce Christopher J. , Valant Celine , Christopoulos Arthur , Thal David M.
Published: September 2024

The activation of a G protein–coupled receptor (GPCR) leads to the formation of a ternary complex between agonist, receptor, and G protein that is characterized by high-affinity binding. Allosteric modulators bind to a distinct binding site from the orthosteric agonist and can modulate both the affinity and the efficacy of orthosteric agonists. The influence allosteric modulators have on the high-affinity active state of the GPCR-G protein ternary complex is unknown due to limitations on attempting to characterize this interaction in recombinant whole cell or membrane-based assays. Here, we use the purified M
2
muscarinic acetylcholine receptor reconstituted into nanodiscs to show that, once the agonist-bound high-affinity state is promoted by the G protein, positive allosteric modulators stabilize the ternary complex that, in the presence of nucleotides, leads to an enhanced initial rate of signaling. Our results enhance our understanding of how allosteric modulators influence orthosteric ligand signaling and will aid the design of allosteric therapeutics.
Substrate dependence of transport coupling and phenotype of a small multidrug resistance transporter in
Pseudomonas aeruginosa
Authors: Wegrzynowicz Andrea K. , Heelan William J. , Demas Sydnye P. , McLean Maxwell S. , Peters Jason M. , Henzler-Wildman Katherine A.
Published: September 2024

Small multidrug resistance (SMR) transporters are key players in the defense of multidrug-resistant pathogens to toxins and other homeostasis-perturbing compounds. However, recent evidence demonstrates that EmrE, an SMR from
Escherichia coli
and a model for understanding transport, can also induce susceptibility to some compounds by drug-gated proton leak. This runs down the ∆pH component of the proton-motive force (PMF), reducing the viability of the affected bacteria. Proton leak may provide an unexplored drug target distinct from the targets of most known antibiotics. Activating proton leak requires an SMR to be merely present, rather than be the primary resistance mechanism, and dissipates the energy source for many other efflux pumps. PAsmr, an EmrE homolog from
Pseudomonas aeruginosa
, transports many EmrE substrates in cells and purified systems. We hypothesized that PAsmr, like EmrE, may confer susceptibility to some compounds via drug-gated proton leak. Growth assays of
E. coli
expressing PAsmr displayed substrate-dependent resistance and susceptibility phenotypes, and
in vitro
solid-supported membrane electrophysiology experiments revealed that PAsmr performs both antiport and substrate-gated proton uniport, demonstrating the same functional promiscuity observed in EmrE. Growth assays of
P. aeruginosa
strain PA14 demonstrated that PAsmr contributes resistance to some antimicrobial compounds, but no growth defect is observed with susceptibility substrates, suggesting
P. aeruginosa
can compensate for the proton leak occurring through PAsmr. These phenotypic differences between
P. aeruginosa
and
E. coli
advance our understanding of the underlying resistance mechanisms in
P. aeruginosa
and prompt further investigation into the role that SMRs play in antibiotic resistance in pathogens.

IMPORTANCE

Small multidrug resistance (SMR) transporters are a class of efflux pumps found in many pathogens, although their contributions to antibiotic resistance are not fully understood. We hypothesize that these transporters may confer not only resistance but also susceptibility, by dissipating the proton-motive force. This means to use an SMR transporter as a target; it merely needs to be present (as opposed to being the primary resistance mechanism). Here, we test this hypothesis with an SMR transporter found in
Pseudomonas aeruginosa
and find that it can perform both antiport (conferring resistance) and substrate-gated proton leak. Proton leak is detrimental to growth in
Escherichia coli
but not
P. aeruginosa
, suggesting that
P. aeruginosa
responds differently to or can altogether prevent ∆pH dissipation.
Collaborative learning in the digital age: empowering tuberculosis researchers through virtual training
Authors: Dippenaar Anzaan , Sylvester Taime , Ealand Christopher , Ismail Nabila , Rakotosamimanana Niaina , Miller Michele , Kana Bavesh D. , Warren Rob M. ,   for the FSPI Consortium
Published: September 2024

Integrating whole genome sequencing (WGS) of the
Mycobacterium tuberculosis
complex into routine care, surveillance, and research in high tuberculosis burden settings remains challenging due to limited resources and skills. While technological platforms for scaling WGS are emerging, scaling wet lab and analytic components often depends on partnerships where such skills have been established. To address this, a virtual training program was developed. Over 12 weeks, 21 trainees from five Southern African institutes engaged in learning from curated theoretical content and interactive virtual meetings with experienced instructors. The training program, developed by a diverse team of experts in molecular biology, biomedical research, microbiology, and tuberculosis research, provided comprehensive coverage aligned with the latest advancements. Teaching strategies included interactive mentor-led sessions and real-time feedback, together with facilitated knowledge exchange and understanding. The virtual training program yielded several successes. Of note, trainees submitted three scientific articles for peer review, based on their acquired knowledge and its application in research. The program also fostered collaborations on
Mycobacterium tuberculosis
WGS among participants, showcasing the potential for networking and future joint projects. While the virtual training program encountered challenges related to the pandemic, limited resources, trainee engagement, and language barriers, these were creatively mitigated. To improve future training sessions, a platform assessing participant engagement and information retention is recommended. Wider collaborative efforts among experts and institutions in collating resources will lead to more comprehensive training programs. Addressing challenges such as internet connectivity issues and language barriers is crucial for ensuring inclusivity and enhancing the overall learning experience. In conclusion, the virtual training program successfully provided knowledge and skill training in WGS to trainees, leading to scientific article submissions and collaborations. Furthermore, content creators benefited from improved science communication and training opportunities.
Genomic transfer via membrane vesicle: a strategy of giant phage phiKZ for early infection
Authors: Antonova Daria , Nichiporenko Anna , Sobinina Mariia , Wang Yueqi , Vishnyakov Innokentii E. , Moiseenko Andrey , Kurdyumova Inna , Chesnokov Yuri M. , Stepanchikova Elizaveta , Bourkaltseva Maria , Samygina Valeriya R. , Khodorkovskii Mikhail , Sokolova Olga S. , Yakunina Maria V.
Published: September 2024

During infection, the giant phiKZ phage forms a specialized structure at the center of the host cell called the phage nucleus. This structure is crucial for safeguarding viral DNA against bacterial nucleases and for segregating the transcriptional activities of late genes. Here, we describe a morphological entity, the early phage infection (EPI) vesicle, which appears to be responsible for earlier gene segregation at the beginning of the infection process. Using cryo-electron microscopy, electron tomography (ET), and fluorescence microscopy with membrane-specific dyes, we demonstrated that the EPI vesicle is enclosed in a lipid bilayer originating, apparently, from the inner membrane of the bacterial cell. Our investigations further disclose that the phiKZ EPI vesicle contains both viral DNA and viral RNA polymerase (vRNAP). We have observed that the EPI vesicle migrates from the cell pole to the center of the bacterial cell together with ChmA, the primary protein of the phage nucleus. The phage DNA is transported into the phage nucleus after phage maturation, but the EPI vesicle remains outside. We hypothesized that the EPI vesicle acts as a membrane transport agent, efficiently delivering phage DNA to the phage nucleus while protecting it from the nucleases of the bacterium.

IMPORTANCE

Our study shed light on the processes of phage phiKZ early infection stage, expanding our understanding of possible strategies for the development of phage infection. We show that phiKZ virion content during injection is packed inside special membrane structures called early phage infection (EPI) membrane vesicles originating from the bacterial inner cell membrane. We demonstrated the EPI vesicle fulfilled the role of the safety transport unit for the phage genome to the phage nucleus, where the phage DNA would be replicated and protected from bacterial immune systems
Characterization of HPV6/11-reactive T-cell subsets in papillomas of patients with juvenile-onset recurrent respiratory papillomatosis and identification of HPV11 E7-specific candidate TCR clonotypes
Authors: Peng Yun , Wang Wei , Liu Xiangjun , Li Shilan , Zhang Jie , Ni Xin , Gui Jingang
Published: September 2024

Juvenile-onset recurrent respiratory papillomatosis (JORRP) is caused by persistent infection of epithelial cells by low-risk human papillomavirus (HPV) types 6 and 11. While multiple infiltrated immune cells have been reported to mediate disease progress, knowledge of HPV-reactive T-cell subsets in papillomas remains elusive. Through single-cell RNA sequencing and RNA microarray, we found that CD8+ tissue-resident memory T (CD8+ T
RM
) cells with strong interferon-gamma (IFN-γ) production expanded, and were negatively correlated to the disease severity in the frequency of surgery. These IFN-γ+ CD8+ memory T cells were readily activated and expanded
in vitro
by autologous dendritic cells loaded with HPV11 E7 peptide pool. Moreover, T cell receptor (TCR) clonal expansion was observed in JORRP papilloma tissues, indicating a biased TCR repertoire toward HPV-specific recognition. Finally, we identified and characterized HPV11 E7-specific candidate TCR clonotypes from IFN-γ+ CD8+ memory T cells, suggesting their potential application in TCR-engineered T cells (TCR-T) therapy for HPV11-related diseases. Our findings provided insights into the specific local immune response to HPV6/11 infection and highlighted the importance of IFN-γ+ CD8+ T
RM
cells in anti-HPV6/11 T-cell immunity.

IMPORTANCE

The persistent recurrence of human papillomavirus (HPV) 6/11 infection in papillomas underscores the failure of local immune responses in patients with juvenile-onset recurrent respiratory papillomatosis (JORRP). Our previous study demonstrated that T cells constitute the predominant immune cell population in JORRP papilloma tissues. Understanding the T-cell-mediated immune responses within JORRP papilloma tissues is crucial for disease control. In the present study, we characterized CD8+ tissue-resident memory T (CD8+ T
RM
) cells as the primary T-cell subset responsible for local anti-HPV6/11 immunity. Moreover, we identified two HPV11 E7-specific candidate T cell receptor (TCR) clonotypes out of IFN-γ+ CD8+ memory T cells. Overall, our findings provided insights into the local immune responses to HPV6/11 infection and offered information for developing more effective immunotherapeutic strategies against JORRP.
Supporting caregivers of children living with disability in a humanitarian context: realist-informed evaluation of the ‘Mighty Children’programme in Afghanistan
Authors: Evans Natalie , Ahmadi Noorwhiza , Morgan Alice , Zalmai Sadia , Milner Kate M , Atif Mohamed Faiz , Graham Hamish R
Published: September 2024

Introduction

To ensure that humanitarian action is disability-inclusive, evidence is needed to understand how different strategies to support children living with disabilities and their families can work in these settings. Evidence from other contexts suggests support groups can improve caregiver quality of life (QOL). This study reports an evaluation of the ‘Mighty Children’programme a participatory educational support group programme for caregivers of children living with disability in Kabul province, Afghanistan.

Methods

We conducted a mixed-methods realist-informed before-and-after study to measure change in caregiver-reported QOL and explore how and for whom the programme worked, and in what contexts. Female caregivers of children with any disability were recruited through clinics in urban Kabul (n=3) and rural Paghman district (n=3). We collected quantitative data on QOL pre/post programme using the Paediatric Quality of Life Inventory Family Impact Module (PedsQL-FIM). Qualitative data were collected through facilitator and participant focus groups postprogramme.

Results

118 caregivers participated in two cohorts (November 2020, February 2021). Caregivers expressed a significant increase in QOL from baseline to programme completion (t(125)=−10.7, p≤0.0001). Participation in cohort 2 was associated with the greatest PedsQL-FIM change.

Qualitative data revealed positive changes postprogramme in five key areas: caregiver mindset, parenting practices, disability-inclusive behaviours, psychological well-being and child functioning. These changes were seen as both outcomes and mechanisms influencing the primary outcome of QOL. Mechanisms that mediated these changes included increased knowledge of disability and the core acceptance and commitment therapy components of mindfulness and acceptance.

Conclusion

TheMighty Childrencaregiver support programme for children living with disability in Afghanistan was associated with improved caregiver QOL. Further studies are warranted to explore pathways to scale, sustainability and potential application in other settings.