bluuebunny/crossref_metadata_2025 huggingface dataset:
Population pharmacokinetic analysis of enrofloxacin and its active metabolite ciprofloxacin after intravenous injection to cats with reduced kidney function
Authors: Foster Jonathan D. , Abouraya Mahmoud , Papich Mark G. , Muma Nancy A.
Published: September 2023

Background

It is unknown if enrofloxacin accumulates in plasma of cats with reduced kidney function.

Hypothesis

To determine if enrofloxacin and its active metabolite ciprofloxacin have reduced clearance in azotemic cats.

Animals

Thirty‐four cats hospitalized for clinical illness with variable degree of kidney function.

Methods

Prospective study. After enrofloxacin (dose 5 mg/kg) administration to cats, sparse blood sampling was used to obtain 2 compartment population pharmacokinetic results using nonlinear mixed‐effects modeling. Plasma enrofloxacin and ciprofloxacin concentrations were measured and summed to obtain the total fluoroquinolone concentration. A model of ciprofloxacin metabolism from enrofloxacin was created and evaluated for covariate effects on clearance, volume of distribution, and the metabolic rate of ciprofloxacin generation from enrofloxacin.

Results

Body weight was the only covariate found to affect total fluoroquinolone volume of distribution (effect 1.63, SE 0.19, P < .01) and clearance (effect 1.63, SE 0.27, P < .01). Kidney function did not have a significant effect on total fluoroquinolone clearance (median 440.8 mL/kg/h (range 191.4‐538.0 mL/kg/h) in cats with normal kidney function, 365.8 mL/kg/h (range 89.49‐1092.0 mL/kg/h) in cats with moderate kidney dysfunction, and 308.5 mL/kg/h (range 140.20‐480.0 mL/kg/h) in cats with severe kidney dysfunction (P = .64). Blood urea nitrogen concentration influenced the metabolic generation of ciprofloxacin from enrofloxacin (effect 0.51, SE 0.08, P < .01), but other markers of kidney function did not.

Conclusions and clinical importance.

Adjustment of enrofloxacin dosage is not indicated for azotemic cats.
Unravelling the trophic guild structure of Neotropical Carnivora: diet specialisations, spatial variation and phylogenetic drivers
Authors: Metz Lorena , Monteiro‐Filho Emygdio Leite de Araujo , Fusco‐Costa Roberto , D'Bastiani Elvira , Padial Andre Andrian
Published: September 2023

Carnivora species present specialisations for carnivorous diet, although their dietary spectrum is variable: some are strictly carnivorous, others feed mostly on plants. Knowledge about Carnivora feeding habits and resource use patterns is the basis for understanding ecological dynamics, including their role in ecosystems, trophic interactions and conservation.

We aimed to contribute to the identification and description of the trophic guild structure of Carnivora species throughout the Neotropical Region and explore the main drivers behind their structuring.

We compiled Carnivora dietary studies and evaluated trophic guild formation through network analysis, diet dissimilarity and overlapping. We investigated whether there is spatial variation in diet parameters and the role of phylogeny in trophic guild structuring.

We found dietary studies for 32 species from six Carnivora families. We observed two important biases: most studies focus on large‐bodied felids and canids and were predominantly conducted in South and South‐eastern regions of South America. Additionally, it has been noted that biomes such as the Amazon and Caatinga require further research on dietary studies.

The network patterns evidenced that central items in carnivorans' diet are small mammals, plants, arthropods and crustaceans. Modularity suggests grouping generalists/opportunists, marine‐based, plant‐based and two mammal‐based diets. Most opportunistic and generalist species were found within the families Canidae and Procyonidae, while felids were strictly carnivorous.

Dietary parameters reveal carnivorans tend to maintain niche breadth regardless of the ecoregion, possibly by substitution of items in their diet. Finally, we observed that phylogeny is an important driver of dietary patterns, indicating that evolutionary history explains part of the habits of carnivores. Our review provides insights to identify broad‐scale patterns and guidelines for new studies.
Role of phenotypic and transcriptomic plasticity in alpine adaptation of Arabidopsis arenosa
Authors: Wos Guillaume , Požárová Doubravka , Kolář Filip
Published: September 2023

Plasticity is an important component of the response of organism to environmental changes, but whether plasticity facilitates adaptation is still largely debated. Using transcriptomic and phenotypic data, we explored the evolution of ancestral plasticity during alpine colonization in Arabidopsis arenosa. We leveraged naturally replicated adaptation in four distinct mountain regions in Central Europe. We sampled seeds from ancestral foothill and independently formed alpine populations in each region and raised them in growth chambers under conditions approximating their natural environments. We gathered RNA‐seq and genetic data of 48 and 63 plants and scored vegetative and flowering traits in 203 and 272 plants respectively. Then, we compared gene expression and trait values over two treatments differing in temperature and irradiance and elevations of origin and quantified the extent of ancestral and derived plasticity. At the transcriptomic level, initial plastic changes tended to be more reinforced than reversed in adapted alpine populations. Genes showing reinforcement were involved in the stress response, developmental processes and morphogenesis and those undergoing reversion were related to the stress response (light and biotic stress). At the phenotypic level, initial plastic changes in all but one trait were also reinforced supporting a facilitating role of phenotypic plasticity during colonization of an alpine environment. Our results contrasted with previous studies that showed generally higher reversion than reinforcement and supported the idea that ancestral plasticity tends to be reinforced in the context of alpine adaptation. However, plasticity may also be the source of potential maladaptation, especially at the transcriptomic level.
Vomiting after intrathecal chemotherapy under anesthesia in pediatric patients with hematologic cancers: A cohort study
Authors: França de Moraes Gustavo Henrique , Lima Luciana Cavalcanti , Couceiro Tania Cursino de Menezes , Lins Mecneide Mendes , Cumino Débora de Oliveira , Simões Leonardo Augusto Barbosa Magalhães , Mello Maria Júlia Gonçalves de
Published: September 2023

Introduction

Despite preventive strategies, vomiting is an adverse event affecting patients with cancer. However, literature on the incidence and risk factors for vomiting in pediatric patients with cancer are scarce.

Aim

To assess the incidence and risk factors for vomiting within 24 h and goodness of fit for the Eberhart score in pediatric patients with hematologic cancers after receiving intrathecal chemotherapy under deep sedation.

Methods

This prospective cohort study included patients under 20 years of age with hematologic cancers who were scheduled to undergo intrathecal chemotherapy under anesthesia. The primary outcome was the occurrence of vomiting within 24 h after the end of anesthesia. Sociodemographic and procedure data and underlying diseases were collected. Patients were monitored during the procedure, in the postanesthesia care unit, and the day after (by phone call).

Results

A total of 139 patients were included, and the incidence of vomiting was 30.9% within 24 h after intrathecal chemotherapy under anesthesia, with 90.7% of vomiting prior to 6 h. Prophylactic ondansetron was administered prior to the procedure to 45.3% of patients. Risk factors for vomiting were female gender (hazard ratio: 2.47, 95% confidence interval: 1.35–4.53, p: .003), consolidation phase of treatment (hazard ratio: 2.16, 95% confidence interval: 1.10–4.24, p: .025), and history of kinetosis (hazard ratio: 2.49, 95% confidence interval: 1.31–4.70, p: .005). Incidence of vomit was higher than estimated by the Eberhart score distribution (observed incidence in patients with a score of zero: 33.3%; with a score of one: 28.8%; with a score of two: 60%).

Conclusion

A high incidence of vomiting was observed within 24 h after intrathecal chemotherapy under propofol deep sedation. Risk factors for this outcome were established (being female, consolidation phase of treatment, and previous kinetosis), and evidence suggested that the Eberhart score was not suitable for the studied population.
Validity of the modified‐Distraction‐Short‐Scale and Verbal‐Numeric‐Anxiety‐Fear‐Rating‐Scale for children in a preoperative setting
Authors: Proczkowska Marie , Ericsson Elisabeth
Published: September 2023

Background

The perioperative period can be stressful for children and families. Minimizing child distress and investigating the quality of anesthetic care is important. There is a paucity of assessment tools available to assess perioperative anxiety in children.

Aim

To determine the validity and reliability of the modified‐Distraction‐Short‐Scale and the Verbal‐Numeric‐Anxiety‐Fear‐Rating‐Scale in a perioperative setting for children.

Methods

Children (n = 189, 3–12 years old) scheduled for ear, nose, and throat surgery had their anxiety rated at induction by a registered nurse anesthetist. Two observers individually evaluated video recordings of the perioperative period. The Verbal‐Numeric‐Anxiety‐Fear‐Rating‐Scale was used to assess the children's preoperative anxiety and fear, and the modified‐Distraction‐Short‐Scale was used to evaluate coping behavior. The modified‐Yale‐Preoperative‐Anxiety‐Scale was used to measure preoperative anxiety and behavioral compliance during anesthesia induction.

Results

Interrater reliability showed excellent agreement between observers on modified‐Distraction‐Short‐Scale scores (weighted kappa (Kw) = 0.91) and Verbal‐Numeric‐Anxiety‐Fear‐Rating‐Scale (Kw = 0.84). The agreements between the registered nurse anesthetist and observers were moderately good for modified‐Distraction‐Short‐Scale (Kw = 0.65–0.80) and Verbal‐Numeric‐Anxiety‐Fear‐Rating‐Scale scores (Kw = 0.65–0.75). The intraclass correlation coefficient (ICC) for the registered nurse anesthetist and two observers was excellent for modified‐Distraction‐Short‐Scale scores (ICC = 0.96) and Verbal‐Numeric‐Anxiety‐Fear‐Rating‐Scale (ICC = 0.90). Regarding concurrent validity, modified‐Distraction‐Short‐Scale and Verbal‐Numeric‐Anxiety‐Fear‐Rating‐Scale scores were strongly correlated among all three observers (Spearman's correlation coefficient [rs] = 0.75–0.82). The modified‐Yale‐Preoperative‐Anxiety‐Scale scores were moderately correlated with modified‐Distraction‐Short‐Scale (rs = 0.57–0.66) and Verbal‐Numeric‐Anxiety‐Fear‐Rating‐Scale scores (rs = 0.54–0.67). Construct validity was tested by using age as a discriminating variable, and Verbal‐Numeric‐Anxiety‐Fear‐Rating‐Scale, modified‐Distraction‐Short‐Scale, and modified‐Yale‐Preoperative‐Anxiety‐Scale scores were lower for the older age group; however, only modified‐Distraction‐Short‐Scale (Observer 1: p = .035, Observer 2: p = .022), and modified‐Yale‐Preoperative‐Anxiety‐Scale scores were significantly lower (p < .001).

Conclusion

The modified‐Distraction‐Short‐Scale and the Verbal‐Numeric‐Anxiety‐Fear‐Rating‐Scale are simple and valid tools for assessing children's perioperative anxiety or fear and evaluating coping behavior. These results suggest that both scales are useful tools for routine clinical practice and research.
Combinatory ability and heterosis for quantitative traits related to productivity and the pungency in F1 hybrids of habanero pepper (Capsicum chinense Jacq.)
Authors: Rodríguez‐Llanes Yaritza , Pérez‐Brito Daisy , Magaña‐Álvarez Anuar , Cortés‐Velázquez Alberto , Guzmán‐Antonio Adolfo , Mijangos‐Cortés Javier O. , Iglesias‐Andreu Lourdes G. , Canto‐Flick Adriana , Pijeira‐Fernández Gema , Santana‐Buzzy Nancy
Published: September 2023

The objective of this work was to obtain high‐yielding F1 hybrids of the habanero pepper, using 10 outstanding parents in a line‐tester genetic design. General combinatorial ability and specific combinatorial ability were evaluated in the parents' and the hybrids F1 obtained, respectively. Heterosis was determined in the 18 hybrids obtained. The technique of HPLC was used to evaluate the capsaicin content in the fruit of 10 parents and 18 hybrids of habanero pepper. The DNA profiles were analysed as part of the characterization of the germplasm of the species conserved at the CICY. Furthermore, the molecular variation of the genotypes under investigation was assessed using eight SSR and nine ISSR markers. The results showed the presence of substantial morphoagronomic and molecular variability among the habanero pepper genotypes evaluated. Genetic similarities of 83%–93% between parents and 76%–94% between hybrids were found. The most productive hybrids were H8, H10 and H19 with 3.13 to 4.29 kg/plant, respectively, these came from crosses where RNJ‐04 (P26) as the male parent and the hybrid H60 (4.92 kg/plant) that comes from the male parent RES‐08 (P30). Likewise, the H7 hybrid had the highest capsaicin content (128.41 mg/g dry weight, 960,687.00 SHU). Hybrids H43 with 114.39 mg/g DW and 90,444.30 SHU, and H51 with 11.61 mg/g DW and 934,745.07 SHU respectively, also stood out.
Protective effect of Helianthus annuus seed byproduct extract on ultraviolet radiation‐induced injury in skin cells
Authors: Mo Xiaoying , Chen Xiaochun , Pan Xiaojiao , Lu Yantong , Pan Guangjuan , Xie Jielan , Pan Zhenzhen , Li Li , Tian Hui , Li Yaohua
Published: September 2023

Helianthus annuus seed byproduct is a residual product obtained after seed oil extraction. The present study investigated the preventive and repair effects of the H. annuus seed byproduct ethanol extract (HSE) on ultraviolet radiation (UVR)‐induced injury in human immortalized keratinocytes (HaCaTs) and human skin fibroblasts (HSFs). Results revealed that the total phenolic acid and oligosaccharide content in HSE was >50%. HSE had a stronger preventive effect on UVR‐induced injury than the repair effect. Moreover, phenolic acids were the main active component of HSE mediating the preventative effect. In HaCaTs and HSFs, HSE prevented UVR‐induced injury by inhibiting excessive ROS production. It reduced the secretion of tumor necrosis TNF‐α, IL‐1α, IL‐1β, IL‐6, and IL‐8 by inhibiting the level of ROS, thus reducing inflammation‐mediated injury to skin cells. In addition, HSE inhibited the expression of various mRNA kinases in the MAPK–ERK/p38/JNK pathway. This downregulated the expression of activator protein‐1 (AP‐1) mRNA and further reduced the secretion of matrix metalloproteinase (MMP)‐1, MMP‐3, and MMP‐9 as well as reduced UVR‐induced injury to the cells. In conclusion, HSE is a broad‐spectrum, natural UV filter with high efficiency and low toxicity that has the potential to be used in sunscreen products.
Association between longitudinal changes in striatal dopamine transporter uptake and clinical features of dementia with Lewy bodies
Authors: Yamamoto Ryo , Takenoshita Naoto , Inagawa Yuta , Kato Hikaru , Kaneshiro Kyoko , Kamiya Tomoki , Inagawa Shoya , Saisho Aya , Tsugawa Akito , Mastumoto Yukari , Yoshimura Mana , Saito Kazuhiro , Shimizu Soichiro , Sato Tomohiko
Published: September 2023

Background

It is widely known that there is low striatal 123I‐2β‐Carbomethoxy‐3β‐(4‐iodophenyl)‐N‐(3‐ fluoropropyl) nortropane (123I‐FP‐CIT) dopamine transporter single photon emission tomography (DaT‐SPECT) uptake in patients with dementia with Lewy bodies (DLB). No studies to date have analyzed the association between longitudinal changes of clinical features and DaT uptake in patients with Parkinson syndrome, particularly those with DLB. The aim of this study was to investigate the association between the longitudinal changes in DaT uptake and the severity of parkinsonism and cognitive function in DLB patients.

Methods

A total of 35 outpatients with probable DLB who underwent DaT‐SPECT twice (at the initial examination and the follow‐up period) in the Memory Disorder Clinic at the Department of Geriatric Medicine, Tokyo Medical University, were enrolled in this study between April 2014 and September 2020. The correlation between annual changes in DaT uptake and clinical features (cognitive function decline and parkinsonism) of the patients was analyzed.

Results

A significant correlation was detected between annual changes in parkinsonism symptom severity and DaT uptake in the left posterior putamen (r = −0.39, P = 0.03), and between Mini‐Mental State Examination scores and DaT uptake in all regions except the right posterior putamen (P < 0.05) in patients with DLB.

Conclusions

Our results suggested that the pathway from the ventrolateral tier of the substantia nigra to the putamen might be more crucial for motor function than other pathways, not only in Parkinson's disease but also in DLB.
Economic openness, financial bias, and the urban–rural income gap
Authors: Chen Zuocheng , Paudel Krishna P. , Devadoss Stephen
Published: September 2023

We develop a theoretical model to analyze the impact of economic openness and financial bias (i.e., open sector bias and urban area bias) on the urban–rural income gap. Our theoretical model puts forth three propositions, which we empirically test using a dynamic panel data model. We use data from 30 provinces in China spanning from 2004 to 2017 for our empirical analysis. Our results reveal a U‐shaped relationship between the urban–rural income gap and the level of regional economic openness. We also find an inverted U‐shaped relationship between the urban–rural income gap and the open sector bias of regional financial development. Moreover, our analysis indicates a positive relationship between the urban–rural income gap and urban area bias in regional financial development. These three propositions hold true for both nominal and real measures of the income gap.
Experiences of young people living with type 1 diabetes in transition to adulthood: The importance of care provider familiarity and support
Authors: Laursen Mathilde Grøn , Rahbæk Marie Ørts , Jensen Sissel Due , Prætorius Thim
Published: September 2023

Background

During the developmental transition from childhood to adulthood, young people living with type 1 diabetes (T1D) are more likely to take less care of their chronic disease. Alongside the developmental transition, young people with T1D also experience an organisational transition in which the care responsibility changes from a family‐based approach in paediatric care to an individualised approach in adult care. Little is known from the perspective of the young people about what their interactions with the healthcare providers mean during these transitions.

Aim

The aim of this study is to explore how young people living with T1D experience interactions with their care providers, and what it means for their developmental transition.

Method

Semi‐structured interviews with 10 respondents aged 18–20 living with T1D who were recruited from a youth outpatient diabetes clinic in Denmark. Recorded audio data were transcribed and analysed using an interpretative phenomenological analysis approach.

Results

Young people experience continuity in the relationship with the diabetes nurse from the paediatric clinic and a personal patient–provider relationship with their well‐known and new care providers. This creates a feeling of familiarity and contributes to a seamless transition. The young people express that becoming more involved in diabetes treatment increases their willingness to take more responsibility for their own health. They also express that care providers should support them in managing their diabetes and talk about sensitive topics.

Conclusion

Continuity in the relationship with the diabetes nurse makes the transition from paediatric to adult care more satisfying and seamless. To support the developmental transition, care providers should gradually involve young people more in diabetes management and be supportive as they become more independent during the developmental transition.
Perceptions And Challenges Of Nursing Students Related To Online Learning During COVID-19 in Guyana.-A mixed method study
Authors: Paul Rani , Stephanas Lois
Published: September 2023

Objective: To explore the nursing students’ perceptions and experiences of online learning during the COVID-19 Pandemic- a mixed method. Methods: A mixed method was used and obtained ethical approval from IRB. Quantitatively 419 nursing students’ perceptions were assessed using a valid and reliable Likert scale with 37 items through google form survey.  Qualitatively five focus group discussions (6 to 8 students each) with duration of 60 to 90 minutes from respective five Schools of nursing were conducted via zoom and recorded. Codes were generated using MAXQDA analytics Pro 2022 version 22.2.1.   Results: 276 (65.87%) students agreed self-discipline is necessary for online learning. 267 (63.72%) students strongly agree that online classes reduce travel expenses. Gender had no influence on perception. Younger students showed more positive perception than older students, Senior BSN students showed positive perception compared to RN students and associations are statistically significant at <0.001. Thematic analysis led to the following themes. Some preferred online learning due to its “flexibility” “Convenient” and “access to recorded sessions” and others preferred face to face: online learning is “good for theory only”, but for practical sessions face to face interactions is necessary, “Sense of isolation” “No student interaction” “less student- faculty interaction”. Barriers identified were “internet connectivity issues”, “Electricity issues” and “Technological issues”. Facilitators were “convenience” “reduced cost in transportation” “saves time” and opportunity to become “tech savvy”. Conclusion: Online classes are suitable for theoretical aspects but require face to face interaction for practical components. Key words: perceptions, online learning, nursing students.
Calidad de vida de pacientes de un programa integral de enfermedad pulmonar obstructiva crónica en Bogotá (Colombia)
Authors: Rodriguez Torres Fanny Paola , Giraldo Leiva Dulfay , Arias Guzmán Jorge
Published: September 2023

Introducción: La enfermedad pulmonar obstructiva crónica (EPOC) ocasiona afectaciones en múltiples dimensiones de la calidad de vida de los pacientes. Objetivo: Describir la percepción de calidad de vida de un grupo de pacientes de un programa de atención integral de EPOC de una institución de cuidado primario ambulatorio en Bogotá (Colombia). Metodología: Estudio transversal, realizado en pacientes con EPOC severo y muy severo (n = 1066), a quienes se les aplicó el Cuestionario Saint George (SG) para evaluar su calidad de vida. El análisis estadístico se llevó a cabo por medio de estadística paramétrica para establecer la correlación cuantitativa de la población al ingreso y al año de estancia en el programa. Resultados: el 52,6 % son hombres; edad mediana: 74 años; mejoría en el puntaje global de calidad de vida (SG) de 8,46 puntos después de 12 meses de ingresar al programa (55,68 versus 47,22; p < 0,001). Las dimensiones con cambios significativos fueron las de síntomas e impacto (p < 0,001). En la dimensión actividad no se observaron cambios con significancia clínica (p = 0,07). Conclusiones: La mejoría en el puntaje global de calidad de vida del cuestionario SG de los pacientes que ingresaron a un programa de atención integral de la EPOC confirma la importancia de un abordaje interdisciplinario en el marco de un programa estructurado y multimodal para optimizar su calidad de vida.
.
Dance in Black and White: Examining the Stereotypes of Black and White Ballerinas and Hip-Hop Dancers
Authors: Klein Sydney , Zestcott Colin A. , Brenick Alaina
Published: September 2023

Throughout the course of ballet dance history, White ballerinas have maintained the spotlight—subsequently leaving limited representation of Black ballerinas. However, other forms of dance, such as hip-hop, may yield greater representation of Black dancers due to hip-hop’s origins during the Harlem Renaissance. The current work examined if perceivers stereotype ballet and hip-hop as dance forms more suited for White or Black dancers, respectively. Two hundred sixty-eight online participants completed explicit and implicit (implicit association test) stereotyping measures examining endorsement of the ballet = White and hip-hop = Black stereotypes. In step with predictions, results showed that individuals were more likely to explicitly and implicitly endorse White women as ballerinas and Black women as hip-hop dancers. In addition, participants with ballet and hip-hop dance experience were less likely to endorse the stereotype that ballet dancers are White and hip-hop dancers are Black. Moreover, less stereotype endorsement also predicted greater likelihood of seeing a ballet or hip-hop performance in the future. These findings suggest that perceivers hold expectations about racial identities of dancers in ballet and hip-hop dance. Future directions regarding the role of race and stereotyping in the world of dance and the performing arts are discussed.
Single-cell genotypic and phenotypic analysis of measurable residual disease in acute myeloid leukemia
Authors: Robinson Troy M. , Bowman Robert L. , Persaud Sonali , Liu Ying , Neigenfind Rosemary , Gao Qi , Zhang Jingping , Sun Xiaotian , Miles Linde A. , Cai Sheng F. , Sciambi Adam , Llanso Aaron , Famulare Christopher , Goldberg Aaron , Dogan Ahmet , Roshal Mikhail , Levine Ross L. , Xiao Wenbin
Published: September 2023

Measurable residual disease (MRD), defined as the population of cancer cells that persist following therapy, serves as the critical reservoir for disease relapse in acute myeloid leukemia and other malignancies. Understanding the biology enabling MRD clones to resist therapy is necessary to guide the development of more effective curative treatments. Discriminating between residual leukemic clones, preleukemic clones, and normal precursors remains a challenge with current MRD tools. Here, we developed a single-cell MRD (scMRD) assay by combining flow cytometric enrichment of the targeted precursor/blast population with integrated single-cell DNA sequencing and immunophenotyping. Our scMRD assay shows high sensitivity of approximately 0.01%, deconvolutes clonal architecture, and provides clone-specific immunophenotypic data. In summary, our scMRD assay enhances MRD detection and simultaneously illuminates the clonal architecture of clonal hematopoiesis/preleukemic and leukemic cells surviving acute myeloid leukemia therapy.
An acoustically controlled helical microrobot
Authors: Deng Yong , Paskert Adrian , Zhang Zhiyuan , Wittkowski Raphael , Ahmed Daniel
Published: September 2023

As a next-generation toolkit, microrobots can transform a wide range of fields, including micromanufacturing, electronics, microfluidics, tissue engineering, and medicine. While still in their infancy, acoustically actuated microrobots are becoming increasingly attractive. However, the interaction of acoustics with microstructure geometry is poorly understood, and its study is necessary for developing next-generation acoustically powered microrobots. We present an acoustically driven helical microrobot with a length of 350 μm and a diameter of 100 μm that is capable of locomotion using a fin-like double-helix microstructure. This microrobot responds to sound stimuli at ~12 to 19 kHz and mimics the spiral motion of natural microswimmers such as spirochetes. The asymmetric double helix interacts with the incident acoustic field, inducing a propulsion torque that causes the microrobot to rotate around its long axis. Moreover, our microrobot has the unique feature of its directionality being switchable by simply tuning the acoustic frequency. We demonstrate this locomotion in 2D and 3D artificial vasculatures using a single sound source.
The competition between anthropogenic aerosol and greenhouse gas climate forcing is revealed by North Pacific water-mass changes
Authors: Shi Jia-Rui , Wijffels Susan E. , Kwon Young-Oh , Talley Lynne D. , Gille Sarah T.
Published: September 2023

Modeled water-mass changes in the North Pacific thermocline, both in the subsurface and at the surface, reveal the impact of the competition between anthropogenic aerosols (AAs) and greenhouse gases (GHGs) over the past 6 decades. The AA effect overwhelms the GHG effect during 1950–1985 in driving salinity changes on density surfaces, while after 1985 the GHG effect dominates. These subsurface water-mass changes are traced back to changes at the surface, of which ~70% stems from the migration of density surface outcrops, equatorward due to regional cooling by AAs and subsequent poleward due to warming by GHGs. Ocean subduction connects these surface outcrop changes to the main thermocline. Both observations and models reveal this transition in climate forcing around 1985 and highlight the important role of AA climate forcing on our oceans’ water masses.
X-crossing pneumatic artificial muscles
Authors: Feng Miao , Yang Dezhi , Ren Lei , Wei Guowu , Gu Guoying
Published: September 2023

Artificial muscles are promising in soft exoskeletons, locomotion robots, and operation machines. However, their performance in contraction ratio, output force, and dynamic response is often imbalanced and limited by materials, structures, or actuation principles. We present lightweight, high–contraction ratio, high–output force, and positive pressure–driven X-crossing pneumatic artificial muscles (X-PAMs). Unlike PAMs, our X-PAMs harness the X-crossing mechanism to directly convert linear motion along the actuator axis, achieving an unprecedented 92.9% contraction ratio and an output force of 207.9 Newtons per kilogram per kilopascal with excellent dynamic properties, such as strain rate (1603.0% per second), specific power (5.7 kilowatts per kilogram), and work density (842.9 kilojoules per meter cubed). These properties can overcome the slow actuation of conventional PAMs, providing robotic elbow, jumping robot, and lightweight gripper with fast, powerful performance. The robust design of X-PAMs withstands extreme environments, including high-temperature, underwater, and long-duration actuation, while being scalable to parallel, asymmetric, and ring-shaped configurations for potential applications.
Order-of-magnitude SNR improvement for high-field EPR spectrometers via 3D printed quasi-optical sample holders
Authors: Sojka Antonín , Price Brad D. , Sherwin Mark S.
Published: September 2023

Here, we present a rapidly prototyped, cost-efficient, and 3D printed quasi-optical sample holder for improving the signal-to-noise ratio (SNR) in modern, resonator-free, and high-field electron paramagnetic resonance (HFEPR) spectrometers. Such spectrometers typically operate in induction mode: The detected EPR (“cross-polar”) signal is polarized orthogonal to the incident (“co-polar”) radiation. The sample holder makes use of an adjustable sample positioner that allows for optimizing the sample position to maximize the 240-gigahertz magnetic field
B
1
and a rooftop mirror that allows for small rotations of the microwave polarization to maximize the cross-polar signal and minimize the co-polar background. When optimally tuned, the sample holder was able to improve co-polar isolation by ≳20 decibels, which is proven beneficial for maximizing the SNR in rapid-scan, pulsed, and continuous-wave EPR experiments. In rapid-scan mode, the improved SNR enabled the recording of entire EPR spectra of a narrow-line radical in millisecond time scales, which, in turn, enabled real-time monitoring of a sample’s evolving line shape.
A closed-loop catalytic nanoreactor system on a transistor
Authors: Wang Xuejun , Xia Binbin , Hao Zhuang , Kang Hua , Liu Wentao , Chen Yiheng , Jiang Qunfeng , Liu Jingyuan , Gou Jian , Dong Baijun , Wee Andrew Thye Shen , Liu Yunqi , Wei Dacheng
Published: September 2023

Precision chemistry demands miniaturized catalytic systems for sophisticated reactions with well-defined pathways. An ideal solution is to construct a nanoreactor system functioning as a chemistry laboratory to execute a full chemical process with molecular precision. However, existing nanoscale catalytic systems fail to in situ control reaction kinetics in a closed-loop manner, lacking the precision toward ultimate reaction efficiency. We find an inter-electrochemical gating effect when operating DNA framework-constructed enzyme cascade nanoreactors on a transistor, enabling in situ closed-loop reaction monitoring and modulation electrically. Therefore, a comprehensive system is developed, encapsulating nanoreactors, analyzers, and modulators, where the gate potential modulates enzyme activity and switches cascade reaction “ON” or “OFF.” Such electric field-effect property enhances catalytic efficiency of enzyme by 343.4-fold and enables sensitive sarcosine assay for prostate cancer diagnoses, with a limit of detection five orders of magnitude lower than methodologies in clinical laboratory. By coupling with solid-state electronics, this work provides a perspective to construct intelligent nano-systems for precision chemistry.
TP63 fusions drive multicomplex enhancer rewiring, lymphomagenesis, and EZH2 dependence
Authors: Wu Gongwei , Yoshida Noriaki , Liu Jihe , Zhang Xiaoyang , Xiong Yuan , Heavican-Foral Tayla B. , Mandato Elisa , Liu Huiyun , Nelson Geoffrey M. , Yang Lu , Chen Renee , Donovan Katherine A. , Jones Marcus K. , Roshal Mikhail , Zhang Yanming , Xu Ran , Nirmal Ajit J. , Jain Salvia , Leahy Catharine , Jones Kristen L. , Stevenson Kristen E. , Galasso Natasha , Ganesan Nivetha , Chang Tiffany , Wu Wen-Chao , Louissaint Abner , Debaize Lydie , Yoon Hojong , Dal Cin Paola , Chan Wing C. , Ho Sui Shannan J. , Ng Samuel Y. , Feldman Andrew L. , Horwitz Steven M. , Adelman Karen , Fischer Eric S. , Chen Chun-Wei , Weinstock David M. , Brown Myles
Published: September 2023

Gene fusions involving tumor protein p63 gene (TP63) occur in multiple T and B cell lymphomas and portend a dismal prognosis for patients. The function and mechanisms of TP63 fusions remain unclear, and there is no target therapy for patients with lymphoma harboring TP63 fusions. Here, we show that TP63 fusions act as bona fide oncogenes and are essential for fusion-positive lymphomas. Transgenic mice expressing TBL1XR1::TP63, the most common TP63 fusion, develop diverse lymphomas that recapitulate multiple human T and B cell lymphomas. Here, we identify that TP63 fusions coordinate the recruitment of two epigenetic modifying complexes, the nuclear receptor corepressor (NCoR)—histone deacetylase 3 (HDAC3) by the N-terminal TP63 fusion partner and the lysine methyltransferase 2D (KMT2D) by the C-terminal TP63 component, which are both required for fusion-dependent survival. TBL1XR1::TP63 localization at enhancers drives a unique cell state that involves up-regulation of MYC and the polycomb repressor complex 2 (PRC2) components EED and EZH2. Inhibiting EZH2 with the therapeutic agent valemetostat is highly effective at treating transgenic lymphoma murine models, xenografts, and patient-derived xenografts harboring TP63 fusions. One patient with
TP63
-rearranged lymphoma showed a rapid response to valemetostat treatment. In summary, TP63 fusions link partner components that, together, coordinate multiple epigenetic complexes, resulting in therapeutic vulnerability to EZH2 inhibition.
Pharmacodynamics of ATI-2307 in a rabbit model of cryptococcal meningoencephalitis
Authors: Giamberardino Charles D. , Tenor Jennifer L. , Toffaletti Dena L. , Palmucci Julia R. , Schell Wiley , Boua Jane-Valeriane K. , Marius Choiselle , Stott Katharine E. , Steele Shelby L. , Hope William , Cilla Don , Perfect John R.
Published: September 2023

Cryptococcal meningoencephalitis (CM) is a devastating fungal disease with high morbidity and mortality. The current regimen that is standard-of-care involves a combination of three different drugs administered for up to one year. There is a critical need for new therapies due to both toxicity and inadequate fungicidal activity of the currently available antifungal drugs. ATI-2307 is a novel aryl amidine that disrupts the mitochondrial membrane potential and inhibits the respiratory chain complexes of fungi—it thus represents a new mechanism for direct antifungal action. Furthermore, ATI-2307 selectively targets fungal mitochondria via a fungal-specific transporter that is not present in mammalian cells. It has very potent
in vitro
anticryptococcal activity. In this study, the efficacy of ATI-2307 was tested in a rabbit model of CM. ATI-2307 demonstrated significant fungicidal activity at dosages between 1 and 2 mg/kg/d, and these results were superior to fluconazole and similar to amphotericin B treatment. When ATI-2307 was combined with fluconazole, the antifungal effect was greater than either therapy alone. While ATI-2307 has potent anticryptococcal activity in the subarachnoid space, its ability to reduce yeasts in the brain parenchyma was relatively less over the same study period. This new drug, with its unique mechanism of fungicidal action and ability to positively interact with an azole, has demonstrated sufficient anticryptococcal potential in this experimental setting to be further evaluated in clinical studies.
Contribution of serology in congenital toxoplasmosis diagnosis: results from a 10-year French retrospective study
Authors: Denis Julie , Lemoine Jean-Philippe , L'ollivier Coralie , Deleplancque Anne-Sophie , Fricker Hidalgo Hélène , Pelloux Hervé , Pomares Christelle , Cimon Bernard , Paris Luc , Houzé Sandrine , Villena Isabelle , Villard Odile
Published: September 2023

This study aimed to evaluate different serological strategies for the postnatal diagnosis of congenital toxoplasmosis (CT) and establish a biological algorithm for CT diagnosis. The study analyzed serological data of immunoglobulins M, A, and G (IgM, IgA, IgG) performed by immunoenzymatic and compared immunological profile (CIP) assays in 668 newborns with CT diagnosis across four testing periods: P1 (D0– D10), P2 (D11–D35), P3 (D36–D45), and P4 (>D45). Forty-nine percent of the 668 CT cases were diagnosed during P1 and 34%, 4%, and 12% during P2, P3, and P4, respectively. CIP assays detected neosynthetized IgMs/IgGs in 98% of CT cases diagnosed during P1, while IgMs and IgAs were detected in 90% and 57% of CT cases diagnosed during P2 and in 88% and 67% of diagnoses made during P3, respectively. Detection of neosynthesized IgMs/IgGs, IgMs, and IgAs by immunoassay contributed to CT diagnosis in 81%, 77%, and 60% of cases, respectively. In total, 46% of serum samples were positive for all three parameters, 27% for two, and 27% for one of the three. The study recommends using the CIP assay as standard during P1 for CT diagnosis and IgM and IgA immunoassays after P1. A clinical and biological follow-up in a specialized center with a close collaboration between biologists and clinicians is highly recommended to increase the chances of early diagnosis. Overall, this study provides useful information for the development of a biological algorithm for CT diagnosis, which can aid in early detection and appropriate treatment of this disease.
Naturally acquired functional antibody responses to group A
Streptococcus
differ between major strain types
Authors: McGregor Reuben , Paterson Aimee , Sharma Prachi , Chen Tiffany , Lovell Jarrod R. , Carlton Lauren H. , Steer Andrew C. , Osowicki Joshua , Loh Jacelyn M. S. , Moreland Nicole J.
Published: September 2023

Group A
Streptococcus
(GAS) is a leading human pathogen for which there is no licensed vaccine. Infections are most common in young children and the elderly suggesting immunity accumulates with exposure until immune senescence in older age. Though protection has been postulated to be strain type specific, based on the M-protein (
emm
-type), the antigenic basis of population-level immunity remains poorly understood. Naturally acquired GAS antibody responses were investigated using intravenous immunoglobulin (IVIG), which contains pooled immunoglobulins from thousands of healthy human donors, as a surrogate for population immunity. Functional opsonophagocytic killing assays were conducted with GAS strains (
n
= 6) representing the three major
emm
-pattern types (
emm
12, A-C pattern;
emm
53, D-pattern; and
emm
75, E-pattern). While IVIG induced opsonophagocytic killing of all GAS strains tested, specificity assays showed the profile of protective antibodies differed considerably between
emm
-types. Antibodies targeting the M-protein were a major component of the functional IVIG antibody response for
emm
12 and
emm
53 strains but not for
emm
75 strains. The striking differences in the contribution of M-protein specific antibodies to killing suggest naturally acquired immunity differs between strains from the major
emm-
patterns. This challenges the dogma that M-protein is the primary protective antigen across all GAS straintypes.

IMPORTANCE

Group A
Streptococcus
(GAS) is a globally important pathogen. With the surge of invasive GAS infections that have occurred in multiple countries, contemporaneous with the relaxation of COVID-19 pandemic restrictions, there is increased interest in the mechanisms underpinning GAS immunity. We utilized intravenous immunoglobulin (IVIG), pooled immunoglobulins from thousands of healthy donors, as a surrogate for population-level immunity to GAS, and explored the contribution of strain-specific (M-type specific) antibodies to GAS immunity using functional killing assays. This revealed striking differences between major strain types as to the contribution of strain specific antibodies to killing. For GAS strains belonging to the E pattern group, M-type specific antibodies do not mediate killing and immunity, which contrasts with strains belonging to pattern A–C and D groups. This challenges the historical dogma, originally proposed by Rebecca Lancefield in the 1950–1960s, that the M-protein is the major protective antigen across all GAS strain types.
Unfolding the secrets of microbiome (Symbiodiniaceae and bacteria) in cold-water coral
Authors: Gong Sanqiang , Liang Jiayuan , Jin Xujie , Xu Lijia , Zhao Meixia , Yu Kefu
Published: September 2023

Recent deep-ocean exploration has uncovered a variety of cold-water coral (CWC) ecosystems around the world ocean, but it remains unclear how microbiome is associated with these corals at a molecular levels. This study utilized metabarcoding, tissue section observation, and metatranscriptomes to investigate the microbiome (Symbiodiniaceae and bacteria) of CWC species (
Narella versluys
i,
Heterogorgia uatumani,
and
Muriceides
sp.) from depths ranging from 260 m to 370 m. Warm-water coral (WWC) species (
Acropora pruinosa
,
Pocillopora damicorni
s, and
Galaxea fascicularis
) were used as control groups. Results revealed that CWC host diverse bacteria and Symbiodiniaceae cells were observed in endoderm of CWC tissues. Several new candidate bacterial phyla were found in both CWC and WWC, including Coralsanbacteria, Coralqiangbacteria, Coralgsqaceae, Coralgongineae, etc. Both the 16S rRNA gene sequencing and metatranscriptomes revealed that Actinobacteria and Proteobacteria were abundant bacterial phyla in CWC. At the gene transcription level, the CWC-associated Symbiodiniaceae community showed a low-level transcription of genes involved in photosynthesis, CO
2
fixation, glycolysis, citric acid cycle, while bacteria associated with CWC exhibited a high-level transcription of genes for carbon fixation via the Wood-Lijungdahl pathway, short chain fatty acids production, nitrogen, and sulfur cycles.

IMPORTANCE

This study shed new light on the functions of both Symbiodiniaceae and bacteria in cold-water coral (CWC). The results demonstrated that Symbiodiniaceae can survive and actively transcribe genes in CWC, suggesting a possible symbiotic or parasitic relationship with the host. This study also revealed complete non-photosynthetic CO
2
fixation pathway of bacteria in CWC, as well as their roles in short chain fatty acids production and assimilation of host-derived organic nitrogen and sulfur. These findings highlight the important role of bacteria in the carbon, nitrogen sulfur cycles in CWC, which were possibly crucial for CWC survival in in deep-water environments.
A novel
in vitro
system of supported planar endosomal membranes (SPEMs) reveals an enhancing role for cathepsin B in the final stage of Ebola virus fusion and entry
Authors: Odongo Laura , Habtegebrael Betelihem H. , Kiessling Volker , White Judith M. , Tamm Lukas K.
Published: September 2023

Ebola virus (EBOV) causes a hemorrhagic fever with fatality rates up to 90%. The EBOV entry process is complex and incompletely understood. Following attachment to host cells, EBOV is trafficked to late endosomes/lysosomes where its glycoprotein (GP) is processed to a 19-kDa form, which binds to the EBOV intracellular receptor Niemann-Pick type C1. We previously showed that the cathepsin protease inhibitor, E-64d, blocks infection by pseudovirus particles bearing 19-kDa GP, suggesting that further cathepsin action is needed to trigger fusion. This, however, has not been demonstrated directly. Since 19-kDa Ebola GP fusion occurs in late endosomes, we devised a system in which enriched late endosomes are used to prepare supported planar endosomal membranes (SPEMs), and fusion of fluorescent (pseudo)virus particles is monitored by total internal reflection fluorescence microscopy. We validated the system by demonstrating the pH dependencies of influenza virus hemagglutinin (HA)-mediated and Lassa virus (LASV) GP-mediated fusion. Using SPEMs, we showed that fusion mediated by 19-kDa Ebola GP is dependent on low pH, enhanced by Ca
2+
, and augmented by the addition of cathepsins. Subsequently, we found that E-64d inhibits full fusion, but not lipid mixing, mediated by 19-kDa GP, which we corroborated with the reversible cathepsin inhibitor VBY-825. Hence, we provide both gain- and loss-of-function evidence that further cathepsin action enhances the fusion activity of 19-kDa Ebola GP. In addition to providing new insights into how Ebola GP mediates fusion, the approach we developed employing SPEMs can now be broadly used for studies of virus and toxin entry through endosomes.

IMPORTANCE

Ebola virus is the causative agent of Ebola virus disease, which is severe and frequently lethal. EBOV gains entry into cells via late endosomes/lysosomes. The events immediately preceding fusion of the viral and endosomal membranes are incompletely understood. In this study, we report a novel
in vitro
system for studying virus fusion with endosomal membranes. We validated the system by demonstrating the low pH dependencies of influenza and Lassa virus fusion. Moreover, we show that further cathepsin B action enhances the fusion activity of the primed Ebola virus glycoprotein. Finally, this model endosomal membrane system should be useful in studying the mechanisms of bilayer breaching by other enveloped viruses, by non-enveloped viruses, and by acid-activated bacterial toxins.