bluuebunny/crossref_metadata_2025 huggingface dataset:
Bilateral salpingectomy as an option of permanent contraception at time of caesarean section: A survey of practice
Authors: Noori Nargis , Edwards Laura , Anpalagan Apputhurai , Athavale Ramanand , Burling Michael , Herbst Unine , Brand Alison , Kapurubandara Supuni
Published: September 2023

Background

Opportunistic bilateral salpingectomy during benign gynaecologic surgery is advocated as a risk‐reducing strategy due to the inverse association of epithelial ovarian cancers observed in epidemiological studies in a low‐risk setting. Currently, no formal guidance exists for permanent surgical contraception at time of caesarean section in Australia.

Aims

Our aim was to survey Fellows of the Royal Australian and New Zealand College of Obstetricians and Gynaecologists (RANZCOG) regarding bilateral salpingectomy compared to other procedures offered for permanent contraception at the time of caesarean section.

Materials and Methods

An online survey was utilised to collect clinician demographics, opinions, barriers, and justifications in regard to options of permanent surgical contraception at time of caesarean section.

Results

Bilateral salpingectomy was identified as the most effective method of permanent contraception at time of caesarean section. However, only 62% of respondents offer the procedure as a method of permanent contraception. The two most common reasons for clinicians to offer bilateral salpingectomy at time of caesarean section were evidence suggesting a link between the fallopian tube and gynaecological cancer (80%) and efficacy as a permanent form of contraception (16%). The primary barrier identified by 51% of respondents was perceived increased risk of surgical complications, followed by reasoning that it would not allow the possibility of future tubal reversal.

Conclusion

This study identifies diverse opinions on surgical approach to permanent contraception at time of caesarean section and offered by clinicians of RANZCOG. Further research is required to establish safety profiles and short‐ and long‐term risks of bilateral salpingectomy.
Continuous infusion of cefiderocol in a critically ill patient with continuous venovenous haemofiltration
Authors: Möhlmann Julia E. , van Luin Matthijs , Uijtendaal Esther V. , Zahr Noël , Sikma Maaike A.
Published: September 2023

Cefiderocol is a broad‐spectrum cephalosporin antibiotic and is indicated in patients with difficult‐to‐treat Gram‐negative bacterial infections. Cefiderocol is applied as a 2–4‐times daily prolonged 3‐h infusion. The therapeutic target of cefiderocol suggests that continuous infusion (CI) may be advantageous, since it is more likely to achieve 100% of time of the unbound concentration above the minimal inhibitory concentration (MIC). However, limited information on cefiderocol as CI has been assessed. We present a case of a critically ill 37‐year‐old woman with continuous venovenous haemofiltration (CVVH) treated with a CI of cefiderocol for multidrug‐resistant Pseudomonas aeruginosa. She received 4 g per 24 h, in accordance with the recommendations for the total daily dose during CVVH with an effluent flow rate of 2.1–3 L/h. We evaluated intraperitoneal, plasma arterial pre‐ and postfilter and ultrafiltrate (urine) total cefiderocol concentrations and discussed the pharmacokinetics in respect to the CVVH settings. The predicted unbound plasma concentrations during CI resulted in 6.8–9.5‐fold higher concentrations than the adopted MIC of 2 mg/L for cefiderocol against P. aeruginosa. The optimal time of the unbound concentration >MIC target of cefiderocol was met during the sampling period, suggesting adequate exposure during the total treatment period. The obtained intraperitoneal concentration indicated adequate cefiderocol exposure at the site of infection. Continuous infusion of 4 g cefiderocol per 24 h led to sufficient plasma concentrations in our anuric critically ill patient treated with CVVH. This case is supportive to the use of cefiderocol as continuous infusion.
Matrine exerts an anti‐tumor effect via regulating HN1 in triple breast cancer both in vitro and in vivo
Authors: Guo Qiusheng , Yu Yuan , Tang Wanfen , Zhou Shishi , Lv Xianmei
Published: September 2023

The treatment of triple‐negative breast cancer (TNBC) cannot meet medical needs, and it is urgent to find new drugs for intervention. This study aimed to investigate the anti‐tumor effect of matrine on the proliferation and apoptosis of TNBC cells based on HN1 regulation in vitro and in vivo. TNBC cell lines (MDA‐MB‐453 and HCC‐1806) were treated with varying concentrations of matrine (0, 1.0, 2.0, 3.0, 4.0, and 5.0 mM). CCK‐8, colony formation assay, transwell assay, and flow cytometry assay were employed to detect proliferation, clone formation, invasion, and apoptosis of TNBC cells. Western blot analysis was applied to detect the protein expression of apoptosis HN1. The effects of matrine on tumor growth, protein expression of HN1, and apoptosis in vivo were validated by xenograft tumor models and histology. It was found that matrine inhibited proliferation, colony formation, and invasion and promoted apoptosis of TNBC cells in vitro. HN1 expression was suppressed by matrine. HN1 overexpression perceptibly reversed the above‐mentioned additive effect in vitro. In vivo experiments found that matrine inhibited tumor growth and the expression of HN1 protein but promoted the protein expression of Cleared‐Caspase‐3. Above all, this study demonstrated that matrine inhibited proliferation and promoted apoptosis of TNBC cells via suppressing HN1 expression. Targeting HN1 by matrine may provide new insights into the therapeutic management of patients with TNBC.
Stories in the Mind? The Role of Story‐Based Categorizations in Motion Classification
Authors: Papenmeier Frank , Purcalla Arrufi Juan , Kirsch Alexandra
Published: September 2023

Categorization is fundamental for spatial and motion representation in both the domain of artificial intelligence and human cognition. In this paper, we investigated whether motion categorizations designed in artificial intelligence can inform human cognition. More concretely, we investigated if such categorizations (also known as qualitative representations) can inform the psychological understanding of human perception and memory of motion scenes. To this end, we took two motion categorizations in artificial intelligence, Motion‐RCC and Motion‐OPRA1, and conducted four experiments on human perception and memory. Participants viewed simple motion scenes and judged the similarity of transformed scenes with this reference scene. Those transformed scenes differed in none, one, or both Motion‐RCC and Motion‐OPRA1 categories. Importantly, we applied an equal absolute metric change to those transformed scenes, so that differences in the similarity judgments should be due only to differing categories. In Experiments 1a and 1b, where the reference stimulus and transformed stimuli were visible at the same time (perception), both Motion‐OPRA1 and Motion‐RCC influenced the similarity judgments, with a stronger influence of Motion‐OPRA1. In Experiments 2a and 2b, where participants first memorized the reference stimulus and viewed the transformed stimuli after a short blank (memory), only Motion‐OPRA1 had marked influences on the similarity judgments. Our findings demonstrate a link between human cognition and these motion categorizations developed in artificial intelligence. We argue for a continued and close multidisciplinary approach to investigating the representation of motion scenes.
The neurophysiology of closed‐loop auditory stimulation in sleep: A magnetoencephalography study
Authors: Jourde Hugo R. , Merlo Raphaëlle , Brooks Mary , Rowe Meredith , Coffey Emily B. J.
Published: September 2023

Closed‐loop auditory stimulation (CLAS) is a brain modulation technique in which sounds are timed to enhance or disrupt endogenous neurophysiological events. CLAS of slow oscillation up‐states in sleep is becoming a popular tool to study and enhance sleep's functions, as it increases slow oscillations, evokes sleep spindles and enhances memory consolidation of certain tasks. However, few studies have examined the specific neurophysiological mechanisms involved in CLAS, in part because of practical limitations to available tools. To evaluate evidence for possible models of how sound stimulation during brain up‐states alters brain activity, we simultaneously recorded electro‐ and magnetoencephalography in human participants who received auditory stimulation across sleep stages. We conducted a series of analyses that test different models of pathways through which CLAS of slow oscillations may affect widespread neural activity that have been suggested in literature, using spatial information, timing and phase relationships in the source‐localized magnetoencephalography data. The results suggest that auditory information reaches ventral frontal lobe areas via non‐lemniscal pathways. From there, a slow oscillation is created and propagated. We demonstrate that while the state of excitability of tissue in auditory cortex and frontal ventral regions shows some synchrony with the electroencephalography (EEG)‐recorded up‐states that are commonly used for CLAS, it is the state of ventral frontal regions that is most critical for slow oscillation generation. Our findings advance models of how CLAS leads to enhancement of slow oscillations, sleep spindles and associated cognitive benefits and offer insight into how the effectiveness of brain stimulation techniques can be improved.
Revisiting the concept of drug‐resistant epilepsy: A TASK1 report of the ILAE/AES Joint Translational Task Force
Authors: Auvin Stéphane , Galanopoulou Aristea S. , Moshé Solomon L. , Potschka Heidrun , Rocha Luisa , Walker Matthew C. ,   the TASK1 workgroup on drug‐resistant epilepsy of the ILAE/AES Joint Translational Task Force
Published: September 2023

Despite progress in the development of anti‐seizure medications (ASMs), one third of people with epilepsy have drug‐resistant epilepsy (DRE). The working definition of DRE, proposed by the International League Against Epilepsy (ILAE) in 2010, helped identify individuals who might benefit from presurgical evaluation early on. As the incidence of DRE remains high, the TASK1 workgroup on DRE of the ILAE/American Epilepsy Society (AES) Joint Translational Task Force discussed the heterogeneity and complexity of its presentation and mechanisms, the confounders in drawing mechanistic insights when testing treatment responses, and barriers in modeling DRE across the lifespan and translating across species. We propose that it is necessary to revisit the current definition of DRE, in order to transform the preclinical and clinical research of mechanisms and biomarkers, to identify novel, effective, precise, pharmacologic treatments, allowing for earlier recognition of drug resistance and individualized therapies.
Factors associated with life‐space mobility restriction in home‐care older adults receiving home‐visit rehabilitation: A cross‐sectional multi‐center study in Japan
Authors: Sugita Yuta , Ohnuma Takeshi , Kogure Eisuke , Hara Tsuyoshi
Published: September 2023

Aim

Life‐space mobility (LSM) restriction is a serious issue among older adults using home‐visit rehabilitation (HR). This study evaluated physical function, transportation, and other factors not comprehensively tested in previous studies and examined factors associated with the restriction of LSM among older adults using HR.

Methods

This cross‐sectional multi‐center study recruited 88 HR users (49 men, 39 women, mean age 79.0 [±7.8] years) living in urban and rural areas from August to October 2020. We administered the Life‐Space Assessment (LSA), the Self‐Efficacy Scale on Going out among community‐dwelling Elderly (SEGE), grip strength, a 30‐s chair stand test, Bedside Mobility Scale, Functional Independence Measure, Frenchay Activities Index (FAI), Ikigai‐9, and Home and Community Environment (HACE) test. Participants were divided into two groups based on the cut‐off value of the LSA scores. In the logistic regression analysis, the dependent variable was LSA scores ≤30, and the independent variables were measured based on objective evaluation items and adjusted for confounding factors (age, sex, and frequency of use of day‐care services).

Results

Restriction of LSM was significantly associated with FAI (odds ratio [OR] = 0.817, 95% confidence interval [CI] = 0.706–0.945), HACE facilitators (OR = 1.558, 95% CI = 1.168–2.079), and living alone (OR = 12.822, 95% CI = 1.202–136.716).

Conclusion

Restriction of LSM is associated with environmental factors, such as assistive devices and household composition, and ability to engage in instrumental activities of daily living. Our findings indicate a great need for focusing on these factors among home‐care older adults receiving HR. Geriatr Gerontol Int 2023; 23: 722–728.
Effect of TiO2 doping on the fracture toughness and thermal conductivity of HfO2 ceramic
Authors: Li Chun , Tang Jun , Ni Liyong , Yang Zhenxiao , Qu Dong , Liu Xiaochen , Gao Chao , Yan Xue
Published: September 2023

Hafnia‐based ceramic coating is considered one of the candidates to substitute yttria partially stabilized zirconia material as thermal barrier coating working above 1200°C. In this work, a series of TiO2‐doped HfO2 ceramics (Hf1–xTixO2, x = 0%, 5%, 10%, 15%, 20%, and 40%) were fabricated by solid‐state reaction. The microstructure, fracture toughness, and thermal conductivity were systematically investigated. The results show that Hf1–xTixO2 ceramics are comprised of monoclinic HfO2 and orthorhombic HfTiO4 phases when Ti4+ doping amount is between 5% and 20%, and the weight fraction of HfTiO4 phase linearly increases with the Ti4+ content and finally reaches 100% for Hf0.6Ti0.4O2. The fracture toughness of TiO2‐doped HfO2 ceramic is higher than 1.75 MPa m.5 when TiO2 content is no more than 15% and decreases below 1.5 MPa m0.5 if TiO2 content further increases. The thermal conductivity is significantly decreased by TiO2 doping attributed to the precipitated HfTiO4 phase. Considering the mechanical properties and thermal insulation capacity, the doping of 15% TiO2 would be beneficial for the HfO2‐based ceramics.
Enamel coatings mill additives optimization for sulfuric acid corrosion
Authors: Li Wensheng , Hong Hao , Qu Xuewei , Li Cuixia , Elena Yatsenko
Published: September 2023

Different mill additives were optimized to improve enamel coatings anti sulfuric corrosion, the immersive corrosion behaviors in 30 wt. % H2SO4 solution for 120 days of the above enamel coatings were investigated by X‐ray diffraction, scanning electron microscope‐energy dispersive spectrometer, laser scanning confocal microscope, Raman spectra, open‐circuit potential, and electrochemical impedance spectroscopy techniques. Results showed that the enamel coating with 12 wt. % quartz mill additives presents the best corrosion resistance. The mill additives significantly reduced the porosity, increased the silicon–oxygen network density, enhanced the gel passivation layer formation ability of enamel coatings, increased the alkaline oxide content, and prevented the ion exchange within the sulfuric acid solution.
Trends in use of antipsychotics and psychoactive drugs in older patients after major surgery
Authors: Kim Dae Hyun , Lee Hemin , Pawar Ajinkya , Lee Su Been , Park Chan Mi , Levin Raisa , Metzger Eran , Bateman Brian T. , Ely E. Wesley , Pandharipande Pratik P. , Pisani Margaret A. , Hohmann Samuel F. , Marcantonio Edward R. , Inouye Sharon K.
Published: September 2023

Background

Professional society guidelines recommend limiting the use of antipsychotics in older patients with postoperative delirium. How these recommendations affected the use of antipsychotics and other psychoactive drugs in the postoperative period has not been studied.

Methods

This retrospective cohort study included patients 65 years or older without psychiatric diagnoses who underwent major surgery in community hospitals (CHs) and academic medical centers (AMCs) in the United States. The outcome was the rate of hospital days exposed to antipsychotics, antidepressants, antiepileptics, benzodiazepines, hypnotics, and selective alpha‐2 receptor agonist dexmedetomidine in the postoperative period by hospital type.

Results

The study included 4,098,431 surgical admissions from CHs (mean age 75.0 [standard deviation, 7.1] years; 50.8% female) during 2008–2018 and 2,310,529 surgical admissions from AMCs (75.0 [7.4] years; 49.4% female) during 2009–2018. In the intensive care unit (ICU) setting, the number of exposed days per 1000 hospital‐days declined for haloperidol (CHs: 33–21 days [p < 0.01]; AMCs: 24–15 days [p < 0.01]) and benzodiazepines (CHs: 261–136 days [p < 0.01]; AMCs: 150–77 days [p < 0.01]). The use of atypical antipsychotics, antidepressants, antiepileptics, and dexmedetomidine increased, while hypnotic use varied by the hospital type. In the non‐ICU setting, the rate declined for haloperidol in CHs but not in AMCs (CHs: 10–6 days [p < 0.01]; AMCs: 4–3 days [p = 0.52]) and for benzodiazepines in both settings (CHs: 126–56 days [p < 0.01]; AMCs: 30–27 days [p < 0.01]). The use of antiepileptics and antidepressants increased, while the use of atypical antipsychotics and hypnotics varied by the hospital type.

Conclusions

The use of haloperidol and benzodiazepines in the postoperative period declined at both CHs and AMCs. These trends coincided with the increasing use of other psychoactive drugs.
The taxonomic status, synonymy and nomenclature of Buglossoides rochelii comb. nov. (Boraginaceae), a neglected plant of south‐eastern Europe
Authors: Stoyanov Stoyan S. , Mátis Attila , Sennikov Alexander N.
Published: September 2023

The identity of Lithospermum rochelii, so far known only from its type locality (Bulgaria, hills in Plovdiv town), remained hitherto uncertain. Our examination of its original material and re‐collection of the species from its locus classicus in Plovdiv town revealed its identity with Lithospermum glandulosum (syn. Buglossoides glandulosa) described later from an adjacent area, in the towns of Sadovo and Asenovgrad (Plovdiv Region), and Lithospermum czernjajevii (syn. Buglossoides czernjajevii), described from north‐eastern Ukraine in the 20th century. The diagnostic characters of L. rochelii and related taxa are clarified, and the distribution area of this species is verified and mapped. A lectotype is designated for L. rochelii and a new combination is provided, Buglossoides rochelii. The chromosome number 2n = 2x = 16, the first ever record for the species, confirms its sharp separation from all other members of Buglossoides s.str., for which only the base chromosome number x = 7 has been known.
Clozapine for the treatment of aggressiveness and agitation in advanced dementia
Authors: Michael Arwed E. , Michael Nikolaus , Erfurth Andreas , Kujovic Milenko
Published: September 2023

Background

Distressing behavioural symptoms, particularly agitation and aggressiveness, remain a difficult problem in everyday clinical practice in the treatment of multimorbid patients with dementia. Clozapine may be an effective therapeutic alternative in this context.

Methods

In a retrospective study, patients who had a diagnosis of dementia and had been treated in a specialized geriatric psychiatry unit with clozapine between August 2018 and February 2022 were included, and medical records were systematically reviewed. The Clinical Global Impressions Scale was used to assess improvement, and the Pittsburgh Agitation Scale for symptom reduction. In addition, side effects and clinical features were documented in detail.

Results

A total of 31 patients (median age 82 years) were identified with a mean clozapine dose of 47.2 (SD 35.6) mg. A total of 13 patients tolerated clozapine very well, 10 showed tolerable side effects, and in 10 patients side effects were the reason for stopping clozapine. Behavioural symptoms improved significantly, as indicated by the assessment scores.

Conclusions

In summary, clozapine was effective and well tolerated in 23 patients, suggesting that low‐dose clozapine may help to alleviate the suffering of difficult‐to‐treat multimorbid patients with advanced dementia and their caregivers. However, particular attention should be paid to adverse drug reactions, especially in patients with cardiovascular and pulmonary impairment.
Invasion by the annual grass, Ventenata dubia does not impact mycorrhizal fungal abundance in an endangered prairie
Authors: Sullivan Alexis A. , Bunn Rebecca , Cheeke Tanya E.
Published: September 2023

One of the challenges in ecological restorations is that some native plant species are difficult to reestablish in disturbed or invaded landscapes. Some invasive plant species negatively impact soil biota, such as arbuscular mycorrhizal (AM) fungi, which can lead to feedbacks that facilitate their dominance in a landscape. The winter annual grass, Ventenata dubia, is rapidly invading North American grasslands, however, the effect of its invasion on AM fungi, plant communities, and soil properties is not well known. In a greenhouse and field experiment, we tested (1) whether the abundance of viable AM fungal propagules is altered in soil invaded by V. dubia; (2) how plant community composition, species richness, and/or diversity may be impacted by V. dubia; and (3) whether soil properties, such as pH and organic matter (OM) vary across invasion levels. We found that the effect of V. dubia on the abundance of mycorrhizal propagules varied among sites and did not reduce the species richness or diversity of resident plant communities. Higher canopy cover of V. dubia was associated with higher soil pH and OM, which suggests either V. dubia invasions change these soil properties, or that V. dubia preferentially invades these areas. Our findings suggest V. dubia does not consistently alter above‐ or belowground communities; however, the potential link between V. dubia invasions and soil pH and OM deserves additional investigation. A better understanding of how invasive annual grasses impact plant and soil communities will be useful in informing restoration efforts in landscapes impacted by invasive species.
Adaptive spike threshold dynamics associated with sparse spiking of hilar mossy cells are captured by a simple model
Authors: Trinh Anh‐Tuan , Girardi‐Schappo Mauricio , Béïque Jean‐Claude , Longtin André , Maler Leonard
Published: September 2023

Hilar mossy cells (hMCs) in the dentate gyrus (DG) receive inputs from DG granule cells (GCs), CA3 pyramidal cells and inhibitory interneurons, and provide feedback input to GCs. Behavioural and in vivo recording experiments implicate hMCs in pattern separation, navigation and spatial learning. Our experiments link hMC intrinsic excitability to their synaptically evoked in vivo spiking outputs. We performed electrophysiological recordings from DG neurons and found that hMCs displayed an adaptative spike threshold that increased both in proportion to the intensity of injected currents, and in response to spiking itself, returning to baseline over a long time scale, thereby instantaneously limiting their firing rate responses. The hMC activity is additionally limited by a prominent medium after‐hyperpolarizing potential (AHP) generated by small conductance K+ channels. We hypothesize that these intrinsic hMC properties are responsible for their low in vivo firing rates. Our findings extend previous studies that compare hMCs, CA3 pyramidal cells and hilar inhibitory cells and provide novel quantitative data that contrast the intrinsic properties of these cell types. We developed a phenomenological exponential integrate‐and‐fire model that closely reproduces the hMC adaptive threshold nonlinearities with respect to their threshold dependence on input current intensity, evoked spike latency and long‐lasting spike‐induced increase in spike threshold. Our robust and computationally efficient model is amenable to incorporation into large network models of the DG that will deepen our understanding of the neural bases of pattern separation, spatial navigation and learning.

image

Key points

Previous studies have shown that hilar mossy cells (hMCs) are implicated in pattern separation and the formation of spatial memory, but how their intrinsic properties relate to their in vivo spiking patterns is still unknown.

Here we show that the hMCs display electrophysiological properties that distinguish them from the other hilar cell types including a highly adaptive spike threshold that decays slowly.

The spike‐dependent increase in threshold combined with an after‐hyperpolarizing potential mediated by a slow K+ conductance is hypothesized to be responsible for the low‐firing rate of the hMC observed in vivo.

The hMC's features are well captured by a modified stochastic exponential integrate‐and‐fire model that has the unique feature of a threshold intrinsically dependant on both the stimulus intensity and the spiking history.

This computational model will allow future work to study how the hMCs can contribute to spatial memory formation and navigation.
Variable Thermal Conductivity Metamaterials Applied to Passive Thermal Control of Satellites
Authors: Phoenix Austin A.
Published: September 2023

Active materials like the proposed variable thermal conductivity metamaterial enable new thermal designs and low-cost, low-power, passive thermal control. Thermal control of satellites conventionally requires active thermal control systems that are expensive, large, inefficient, energy-intensive, and unavailable for CubeSats. The high-temperature operation case is the thermal system’s primary design consideration for CubeSats. The thermal path is designed to reject as much heat as possible to ensure the system does not overheat. In other cases, such as during a power anomaly, the oversized thermal path results in rapid cooling, culminating in mission failure due to thermal limits on the electronics or batteries. Improving the thermal control of CubeSats can enable new thermally challenging missions, increase satellite longevity, and increase mission success rate by controlling the dynamic thermal environment. The materials available for thermal management are inherently limited, but new engineered materials provide unique opportunities to change how satellites adapt to thermal loads. This paper investigates using an adaptive metamaterial designed to passively change its thermal conductivity as a function of temperature to meet the needs of the satellite. The thermal performance of a CubeSat is evaluated with a variable thermal conductivity metamaterial located in the critical thermal path from the satellite to the radiator. The system’s performance using two metamaterial configurations is compared to a baseline copper thermal path. Multiple satellite thermal operation cases are investigated to determine the operation ranges, and the metamaterial’s performance in various conditions is quantified.
Kinetostatics of Deployable Concrete Formworks
Authors: Zhao Jing-Shan , Sun Xiao-Cheng , Wei Song-Tao , Lu Wen-Xiu
Published: September 2023

To reform the traditional concrete formwork, an overconstrained deployable frame is designed. It is composed of closed loop deployable units formed by scissor-form elements and orthogonal telescoping rods. Using the reciprocal screw theory, the mobility of the deployable frame is studied, and it has one degree-of-freedom (DoF). To analyze the kinematic performance of the frame in the deployment and folding processes and the static characteristics under external loads at different deployed states, a general approach to analyzing the kinematics and statics by modeling in screw form is proposed. The velocities of joints could be solved in screw coordinates, the position and acceleration of joints could be obtained via a first-order numerical integration and a first-order numerical differential interpolation, respectively. Then, the position information for each joint can be forwarded onto the static equilibrium equations. Through the static analysis at each deployed state, the inner forces in each rod and the active control forces are derived. Kinematics and statics are associated using velocities as the global variable, which allows a unified analysis of mechanisms. This method is computationally highly efficient and also fits for kinematic and static analysis of different kinds of multi-rigid-body mechanisms.
Nondestructively probing the thermodynamics of quantum systems with qumodes
Authors: Elliott Thomas J. , Gu Mile , Thompson Jayne , Liu Nana
Published: September 2023

Quantum systems are by their very nature fragile. The fundamental backaction on a state due to quantum measurement notwithstanding, there is also in practice often a destruction of the system itself due to the means of measurement. This becomes acutely problematic when we wish to make measurements of the same system at multiple times, or generate a large quantity of measurement statistics. One approach to circumventing this is the use of ancillary probes that couple to the system under investigation, and through their interaction, enable properties of the primary system to be imprinted onto and inferred from the ancillae. Here we highlight means by which continuous variable quantum modes (qumodes) can be employed to probe the thermodynamics of quantum systems in and out of equilibrium, including thermometry, reconstruction of the partition function, and reversible and irreversible work. We illustrate application of our results with the example of a spin-1/2 system in a transverse field.
Ableism and assistive technology
Against Technoableism: Rethinking Who Needs Improvement
Ashley Shew
Norton, 2023. 160 pp.
Authors: Berntsen Leslie
Published: September 2023

Harmful tropes can lead to misguided assumptions when designing devices for people with disabilities
Tracking kidney transplant fitness
Authors: Zaidan Mohamad , Lakkis Fadi G.
Published: September 2023

An implantable bioelectronic device detects the early signs of kidney transplant rejection in rats
Chromosomal contacts change with age
Authors: Akbarian Schahram , Won Hyejung
Published: September 2023

The three-dimensional organization of the genome is remodeled throughout life
Transposon sequencing identifies genes impacting
Staphylococcus aureus
invasion in a human macrophage model
Authors: Lo Hsin-Yu , Long Dustin R. , Holmes Elizbeth A. , Penewit Kelsi , Hodgson Taylor , Lewis Janessa D. , Waalkes Adam , Salipante Stephen J.
Published: September 2023

Staphylococcus aureus
is a facultative intracellular pathogen in many host cell types, facilitating its persistence in chronic infections. The genes contributing to intracellular pathogenesis have not yet been fully enumerated. Here, we cataloged genes influencing
S. aureus
invasion and survival within human THP-1 derived macrophages using two laboratory strains (ATCC2913 and JE2). We developed an
in vitro
transposition method to produce highly saturated transposon mutant libraries in
S. aureus
and performed transposon insertion sequencing (Tn-Seq) to identify candidate genes with significantly altered abundance following macrophage invasion. While some significant genes were strain-specific, 108 were identified as common across both
S. aureus
strains, with most (
n
= 106) being required for optimal macrophage infection. We used CRISPR interference (CRISPRi) to functionally validate phenotypic contributions for a subset of genes. Of the 20 genes passing validation, seven had previously identified roles in
S. aureus
virulence, and 13 were newly implicated. Validated genes frequently evidenced strain-specific effects, yielding opposing phenotypes when knocked down in the alternative strain. Genomic analysis of
de novo
mutations occurring in groups (
n
= 237) of clonally related
S. aureus
isolates from the airways of chronically infected individuals with cystic fibrosis (CF) revealed significantly greater
in vivo
purifying selection in conditionally essential candidate genes than those not associated with macrophage invasion. This study implicates a core set of genes necessary to support macrophage invasion by
S. aureus,
highlights strain-specific differences in phenotypic effects of effector genes, and provides evidence for selection of candidate genes identified by Tn-Seq analyses during chronic airway infection in CF patients
in vivo
.
Ribosome heterogeneity results in leader sequence-mediated regulation of protein synthesis in
Francisella tularensis
Authors: Trautmann Hannah S. , Schmidt Sierra S. , Gregory Steven T. , Ramsey Kathryn M.
Published: September 2023

Although ribosomes are generally examined in aggregate, ribosomes can be heterogenous in composition. Evidence is accumulating that changes in ribosome composition may result in altered function, such that ribosome heterogeneity may provide a mechanism to regulate protein synthesis. Ribosome heterogeneity in the human pathogen
Francisella tularensis
results from incorporation of one of three homologs of bS21, a small ribosomal subunit protein demonstrated to regulate protein synthesis in other bacteria. Loss of one homolog, bS21-2, results in genome-wide post-transcriptional changes in protein abundance. This suggests that bS21-2 can, either directly or indirectly, lead to preferential translation of particular mRNAs. Here, we examine the potential of bS21-2 to function in a leader sequence-dependent manner and to function indirectly, via Hfq. We found that the 5´ untranslated region (UTR) of some bS21-2-responsive genes, including key virulence genes, is sufficient to alter translation in cells lacking bS21-2. We further identify features of a 5´ UTR that allow responsiveness to bS21-2. These include an imperfect Shine-Dalgarno sequence and a particular six nucleotide sequence. Our results are consistent with a model in which a bS21 homolog increases the efficiency of translation initiation through interactions with specific leader sequences. With respect to bS21-2 indirectly regulating translation via the RNA-binding protein Hfq, we found that Hfq controls transcript abundance rather than protein synthesis, impacting virulence gene expression via a distinct mechanism. Together, we determined that ribosome composition in
F. tularensis
regulates translation in a leader sequence-dependent manner, a regulatory mechanism which may be used in other bacteria.

IMPORTANCE

Ribosome heterogeneity is common in bacteria, and there is mounting evidence that ribosome composition plays a regulatory role in protein synthesis. However, mechanisms of ribosome-driven gene regulation are not well understood. In the human pathogen
Francisella tularensis
, which encodes multiple homologs for the ribosomal protein bS21, loss of one homolog impacts protein synthesis and virulence. Here, we explore the mechanism behind bS21-mediated changes in protein synthesis, finding that they can be linked to altered translation initiation and are dependent on specific sequences in the leaders of transcripts. Our data support a model in which ribosome composition regulates gene expression through translation, a strategy that may be conserved in diverse organisms with various sources of ribosome heterogeneity.
Structural basis of white-tailed deer,
Odocoileus virginianus
, ACE2 recognizing all the SARS-CoV-2 variants of concern with high affinity
Authors: Han Pu , Meng Yumin , Zhang Di , Xu Zepeng , Li Zhiyuan , Pan Xiaoqian , Zhao Zhennan , Li Linjie , Tang Lingfeng , Qi Jianxun , Liu Kefang , Gao George F.
Published: September 2023

SARS-CoV-2 has been expanding its host range, among which the white-tailed deer (WTD),
Odocoileus virginianus,
became the first wildlife species infected on a large scale and might serve as a host reservoir for variants of concern (VOCs) in case no longer circulating in humans. In this study, we comprehensively assessed the binding of the WTD angiotensin-converting enzyme 2 (ACE2) receptor to the spike (S) receptor-binding domains (RBDs) from the SARS-CoV-2 prototype (PT) strain and multiple variants. We found that WTD ACE2 could be broadly recognized by all of the tested RBDs. We further determined the complex structures of WTD ACE2 with PT, Omicron BA.1, and BA.4/5 S trimer. Detailed structural comparison revealed the important roles of RBD residues on 486, 498, and 501 sites for WTD ACE2 binding. This study deepens our understanding of the interspecies transmission mechanisms of SARS-CoV-2 and further addresses the importance of constant monitoring on SARS-CoV-2 infections in wild animals.

IMPORTANCE

Even if we manage to eliminate the virus among humans, it will still circulate among wildlife and continuously be transmitted back to humans. A recent study indicated that WTD may serve as reservoir for nearly extinct SARS-CoV-2 strains. Therefore, it is critical to evaluate the binding abilities of SARS-CoV-2 variants to the WTD ACE2 receptor and elucidate the molecular mechanisms of binding of the RBDs to assess the risk of spillback events.
The QseB response regulator imparts tolerance to positively charged antibiotics by controlling metabolism and minor changes to LPS
Authors: Hurst Melanie N. , Beebout Connor J. , Hollingsworth Alexis , Guckes Kirsten R. , Purcell Alexandria , Bermudez Tomas A. , Williams Diamond , Reasoner Seth A. , Trent M. Stephen , Hadjifrangiskou Maria
Published: September 2023

The modification of lipopolysaccharide (LPS) in
Escherichia coli
and
Salmonella
spp. is primarily controlled by the two-component system PmrAB. LPS modification allows bacteria to avoid killing by positively charged antibiotics like polymyxin B (PMB). We previously demonstrated that in uropathogenic
E. coli
(UPEC), the sensor histidine kinase PmrB also activates a non-cognate transcription factor, QseB, and this activation somehow augments PMB tolerance in UPEC. Here, we demonstrate—for the first time—that in the absence of the canonical LPS transcriptional regulator, PmrA, QseB can direct some modifications on the LPS. In agreement with this observation, transcriptional profiling analyses demonstrate regulatory overlaps between PmrA and QseB in terms of regulating LPS modification genes. However, both PmrA and QseB must be present for UPEC to mount robust tolerance to PMB. Transcriptional and metabolomic analyses also reveal that QseB transcriptionally regulates the metabolism of glutamate and 2-oxoglutarate, which are consumed and produced during the modification of lipid A. We show that deletion of
qseB
alters glutamate levels in the bacterial cells. The
qseB
deletion mutant, which is susceptible to positively charged antibiotics, is rescued by exogenous addition of 2-oxoglutarate. These findings uncover a previously unknown mechanism of metabolic control of antibiotic tolerance that may be contributing to antibiotic treatment failure in the clinic.

IMPORTANCE

Although antibiotic prescriptions are guided by well-established susceptibility testing methods, antibiotic treatments oftentimes fail. The presented work is significant because it uncovers a mechanism by which bacteria transiently avoid killing by antibiotics. This mechanism involves two closely related transcription factors, PmrA and QseB, which are conserved across
Enterobacterales
. We demonstrate that PmrA and QseB share regulatory targets in lipid A modification pathway and prove that QseB can orchestrate modifications of lipid A in
Escherichia coli
in the absence of PmrA. Finally, we show that QseB controls glutamate metabolism during the antibiotic response. These results suggest that rewiring of QseB-mediated metabolic genes could lead to stable antibiotic resistance in subpopulations within the host, thereby contributing to antibiotic treatment failure.
Sound velocity of eclogite at high pressures and implications for detecting eclogitization in subduction zones
Authors: Zhang Rui , Wang Duojun , Cai Nao , Zhang Jikai , Chen Peng , Han Kenan , Cao Yang
Published: September 2023

The increased velocity associated with decaying seismicity in the subducting oceanic crust usually has been attributed to its eclogitization. However, the degree of the eclogitization of subducting oceanic crust at depth remains unclear due to the lack of velocity data for eclogite at pressures of >3 GPa. In this study, the P- and S-wave velocities of eclogite aggregates composed of omphacite and garnet (Omp100, Omp80Grt20, and Omp50Grt50) were measured simultaneously at pressures of up to 8 GPa using ultrasonic interferometry. The velocities of the eclogite aggregates increased with rising pressure and garnet content. By determining the velocities at different pressures using the finite strain equation, the elastic moduli of the eclogites and their pressure derivatives were determined to be KS0 = 119−134 GPa, KS0′ = 5.2−5.3, G0 = 73−80 GPa, and G0′ = 1.5−1.6. The high-wave velocity and low VP/VS ratio of the eclogites, combined with the seismic tomography and seismicity distribution, jointly constrain the depth and composition of eclogitization in the subducted oceanic crust of Northeast Japan, and a new 1-D velocity structure is proposed. We also compiled and calculated the depth of the eclogitization and the garnet content of the subducting oceanic crusts in 27 typical locations around the Pacific Ocean. The depth of the eclogitization was positively correlated with the age of the subduction zone, and the garnet content was estimated to be 12%−32% in our model.
Assessing household financial burdens for preprimary education and associated socioeconomic inequalities: a case study in China
Authors: Wei Yi , Liu Kai , Kang Le , Behrman Jere R , Richter Linda M , Stein Alan , Song Yingquan , Lu Chunling
Published: September 2023

Background

Providing young children with universal access to preprimary education (PPE) is considered a powerful tool for human capital development and eliminating the intergenerational transmission of poverty. To remove household financial barrier for achieving universal PPE, this study proposed a measure to identify households incurring ‘heavy financial burdens from paying for PPE’ (HBPPE) and conducted a case study in China.

Methods

Using nationally representative data in 2019, we estimated the percentage of households with HBPPE (spent 7% or more of their total annual expenditure) and associated socioeconomic inequalities. We also applied a three-level logit regression model to investigate the factors associated with the probabilities of households incurring HBPPE.

Results

Half of the sampled households spent 7% or more of their expenditures on PPE. Households in the lowest wealth quintile (54%) or households with children attending private PPE (55%) had higher percentages of HBPPE than households in other wealth quintiles (eg, 51% in the highest wealth quintile) or households with children attending public kindergartens (41%). Logit regression analysis shows that the poorest households and households with children attending private kindergarten were more likely to incur HBPPE than their counterparts.

Conclusion

To ensuring universal access to PPE in China, future policy should consider increasing the enrolment of children from low-income families in public kindergartens and increasing governmental investments in low-income households by subsidising children attending PPE.
Inhibition of TCA cycle improves the anti-PD-1 immunotherapy efficacy in melanoma cells via ATF3-mediated PD-L1 expression and glycolysis
Authors: Liu Nian , Yan Mingjie , Tao Qian , Wu Jie , Chen Jing , Chen Xiang , Peng Cong
Published: September 2023

Background

anti-Programmed Death-1 (anti-PD-1) immunotherapy has shown promising manifestation in improving the survival rate of patients with advanced melanoma, with its efficacy closely linked to Programmed cell death-Ligand 1 (PD-L1) expression. However, low clinical efficacy and drug resistance remain major challenges. Although the metabolic alterations from tricarboxylic acid (TCA) cycle to glycolysis is a hallmark in cancer cells, accumulating evidence demonstrating TCA cycle plays critical roles in both tumorigenesis and treatment.

Methods

The plasma levels of metabolites in patients with melanoma were measured by nuclear magnetic resonance (NMR) spectroscopy. The effect of pyruvate dehydrogenase subunit 1 (PDHA1) and oxoglutarate dehydrogenase (OGDH) on immunotherapy was performed by B16F10 tumor-bearing mice. Flow cytometry analyzed the immune microenvironment. RNA sequencing analyzed the global transcriptome alterations in CPI613-treated melanoma cells. The regulation of PD-L1 and glycolysis by PDHA1/OGDH-ATF3 signaling were confirmed by Quantitative real-time polymerase chain reaction (qRT-PCR), western blotting, dual-luciferase reporter gene, Chromatin immunoprecipitation (ChIP)-quantitative PCR and Seahorse assay. The relationship between PDHA1/OGDH-ATF3-glycolysis and the efficacy of melanoma anti-PD-1 immunotherapy was verified in the clinical database and single-cell RNA-seq (ScRNA-Seq).

Results

In our study, the results showed that significant alterations in metabolites associated with glycolysis and the TCA cycle in plasma of patients with melanoma through NMR technique, and then, PDHA1 and OGDH, key enzymes for regulation TCA cycle, were remarkable raised in melanoma and negatively related to anti-PD-1 efficacy through clinical database analysis as well as ScRNA-Seq. Inhibition of PDHA1 and OGDH by either shRNA or pharmacological inhibitor by CPI613 dramatically attenuated melanoma progression as well as improved the therapeutic efficacy of anti-PD-1 against melanoma. Most importantly, suppression of TCA cycle remarkably raises PD-L1 expression and glycolysis flux through AMPK-CREB-ATF3 signaling.

Conclusions

Taken together, our results demonstrated the role of TCA cycle in immune checkpoint blockade and provided a novel combination strategy for anti-PD-1 immunotherapy in melanoma treatment.
Use of genome sequencing to hunt for cryptic second-hit variants: analysis of 31 cases recruited to the 100 000 Genomes Project
Authors: Moore A Rachel , Yu Jing , Pei Yang , Cheng Emily W Y , Taylor Tavares Ana Lisa , Walker Woolf T , Thomas N Simon , Kamath Arveen , Ibitoye Rita , Josifova Dragana , Wilsdon Anna , Ross Alison , Calder Alistair D , Offiah Amaka C , Wilkie Andrew O M ,   Genomics England Research Consortium, Taylor Jenny C , Pagnamenta Alistair T
Published: September 2023

Background

Current clinical testing methods used to uncover the genetic basis of rare disease have inherent limitations, which can lead to causative pathogenic variants being missed. Within the rare disease arm of the 100 000 Genomes Project (100kGP), families were recruited under the clinical indication ‘single autosomal recessive mutation in rare disease’. These participants presented with strong clinical suspicion for a specific autosomal recessive disorder, but only one suspected pathogenic variant had been identified through standard-of-care testing. Whole genome sequencing (WGS) aimed to identify cryptic ‘second-hit’ variants.

Methods

To investigate the 31 families with available data that remained unsolved following formal review within the 100kGP, SVRare was used to aggregate structural variants present in <1% of 100kGP participants. Small variants were assessed using population allele frequency data and SpliceAI. Literature searches and publicly available online tools were used for further annotation of pathogenicity.

Results

Using these strategies, 8/31 cases were solved, increasing the overall diagnostic yield of this cohort from 10/41 (24.4%) to 18/41 (43.9%). Exemplar cases include a patient with cystic fibrosis harbouring a novel exonic LINE1 insertion inCFTRand a patient with generalised arterial calcification of infancy with complex interlinked duplications involving exons 2–6 ofENPP1. Although ambiguous by short-read WGS, theENPP1variant structure was resolved using optical genome mapping and RNA analysis.

Conclusion

Systematic examination of cryptic variants across a multi-disease cohort successfully identifies additional pathogenic variants. WGS data analysis in autosomal recessive rare disease should consider complex structural and small intronic variants as potentially pathogenic second hits.