bluuebunny/crossref_metadata_2025 huggingface dataset:
Measuring the impact of rare diseases in Tasmania, Australia
Authors: Scanlon Philippa , Ridler Garry , Say Genevieve , Kellett Miranda , Charlesworth Jac , Neil Amanda , Dickinson Joanne L. , Burdon Kathryn , Jose Matthew , Wallis Mathew
Published: October 2024

Background

An ongoing challenge with rare diseases is limited data and, consequently, limited knowledge about the collective prevalence and impact of these conditions on individuals, families, and the health system, particularly in rural and regional areas. Using existing datasets, this project aimed to examine the epidemiology of and hospital activity for Tasmanians with rare diseases.

Methods

Rare diseases were defined as non-infectious diseases with a prevalence of less than 1 in 2000. An initial resource set of 1028 ICD-10-AM diagnostic codes was used to identify a cohort of Tasmanians with rare diseases in Tasmanian Health datasets (1 January 2007 until 31 December 2020). Validating the resource set using a small group with known rare diseases revealed limitations in ascertainment, and so an expanded set of 1940 ICD-10-AM diagnostic codes was developed by cross-referencing ICD-10-AM codes with Orphanet data. Cohort hospital activity and admission costs were compared to statewide data for the final year of the study, 01 January 2020 to 31 December 2020.

Results

Using the resource set of 1028 ICD-10-AM diagnostic codes, the period prevalence of rare diseases in Tasmania across all age groups was estimated at 3.5%, with a point prevalence of 1.5% in December 2020. In 2020, 3384 individuals within the Tasmanian rare disease cohort, representing 0.6% of the Tasmanian population, accessed the public hospital system and accounted for 5.6% of all admissions. The mean length of stay for rare disease-related hospital admissions was 5.0 days, compared to 3.3 days for non-rare disease-related admissions. The mean cost per admission for the rare disease cohort was AUD$11,310, compared to AUD$6475 for all admissions statewide. In 2020, using the expanded resource set, the total cost of public hospital admissions in Tasmania was estimated to be AUD$979 million, with rare disease-related hospital admissions accounting for 9.1% of this cost, increasing to 19.0% when the costs for all admissions for the rare disease patients were included.

Conclusions

Patients with rare diseases had more admissions, longer length of stay, and a higher average cost per admission. Patients with rare diseases have a disproportionate impact on statewide hospital activity and costs in Tasmania.
Experiences of mothers of long-term surviving patients with cerebral adrenoleukodystrophy: a qualitative study
Authors: Koto Yuta , Hadano Nozomi , Sakai Norio
Published: October 2024

Background

Adrenoleukodystrophy (ALD) is an X-linked peroxisomal disorder. Its cerebral form presents as a learning and behavioral disorder that, if untreated, leads to rapid neurological regression, disability, and death within 10 years of diagnosis. Therefore, the disease significantly impacts patients’ quality of life, making quality of life assessment crucial for effective medical treatment and care. However, no disease-specific quality of life scale exists for ALD. Therefore, we conducted qualitative research to determine the experiences of patients and their families as a preliminary step toward developing one.

Results

Four mothers of patients with cerebral ALD were interviewed. Based on classification using the qualitative content analysis method, the verbatim transcripts were grouped into four themes: support needs for patients, support needs for families, the impact of treatment, and challenges within support systems.

Conclusions

Support for patients and family members is required after ALD is diagnosed. In addition to addressing symptoms, daily life support and caregiving burden should be considered. Furthermore, several challenges and opportunities exist for improving treatment and support systems. Therefore, combining appropriate supporters and support systems according to the progressive and hereditary characteristics of ALD is crucial.
The prognostic value of radiogenomics using CT in patients with lung cancer: a systematic review
Authors: Jiang Yixiao , Gao Chuan , Shao Yilin , Lou Xinjing , Hua Meiqi , Lin Jiangnan , Wu Linyu , Gao Chen
Published: October 2024

This systematic review aimed to evaluate the effectiveness of combining radiomic and genomic models in predicting the long-term prognosis of patients with lung cancer and to contribute to the further exploration of radiomics. This study retrieved comprehensive literature from multiple databases, including radiomics and genomics, to study the prognosis of lung cancer. The model construction consisted of the radiomic and genomic methods. A comprehensive bias assessment was conducted, including risk assessment and model performance indicators. Ten studies between 2016 and 2023 were analyzed. Studies were mostly retrospective. Patient cohorts varied in size and characteristics, with the number of patients ranging from 79 to 315. The construction of the model involves various radiomic and genotic datasets, and most models show promising prediction performance with the area under the receiver operating characteristic curve (AUC) values ranging from 0.64 to 0.94 and the concordance index (C-index) values from 0.28 to 0.80. The combination model typically outperforms the single method model, indicating higher prediction accuracy and the highest AUC was 0.99. Combining radiomics and genomics in the prognostic model of lung cancer may improve the predictive performance. However, further research on standardized data and larger cohorts is needed to validate and integrate these findings into clinical practice.

Critical relevance statement

The combination of radiomics and genomics in the prognostic model of lung cancer improved prediction accuracy in most included studies.

Key Points

The combination of radiomics and genomics can improve model performance in most studies.

The results of establishing prognosis models by different methods are discussed.

The combination of radiomics and genomics may be helpful to provide better treatment for patients.

Graphical Abstract
Genotype‒phenotype correlation in recessive DNAJB4 myopathy
Authors: Inoue Michio , Jayaraman Divya , Bengoechea Rocio , Bhadra Ankan , Genetti Casie A. , Aldeeri Abdulrahman A. , Turan Betül , Pacheco-Orozco Rafael Adrian , Al-Maawali Almundher , Al Hashmi Nadia , Zamani Ayşe Gül , Göktaş Emine , Pekcan Sevgi , Çağlar Hanife Tuğçe , True Heather , Beggs Alan H. , Weihl Conrad C.
Published: October 2024

Protein aggregate myopathies can result from pathogenic variants in genes encoding protein chaperones. DNAJB4 is a cochaperone belonging to the heat shock protein-40 (HSP40) family and plays a vital role in cellular proteostasis. Recessive loss-of-function variants in DNAJB4 cause myopathy with early respiratory failure and spinal rigidity, presenting from infancy to adulthood. This study investigated the broader clinical and genetic spectrum of DNAJB4 myopathy. In this study, we performed whole-exome sequencing on seven patients with early respiratory failure of unknown genetic etiology. We identified five distinct pathogenic variants in DNAJB4 in five unrelated families of diverse ethnic backgrounds: three loss-of-function variants (c.547 C > T, p.R183*; c.775 C > T, p.R259*; an exon 2 deletion) and two missense variants (c.105G > C, p.K35N; c.181 A > G, p.R61G). All patients were homozygous. Most affected individuals exhibited early respiratory failure, and patients from three families had rigid spine syndrome with axial weakness in proportion to appendicular weakness. Additional symptoms included dysphagia, ankle contractures, scoliosis, neck stiffness, and cardiac dysfunction. Notably, J-domain missense variants were associated with a more severe phenotype, including an earlier age of onset and a higher mortality rate, suggesting a strong genotype‒phenotype correlation. Consistent with a loss of function, the nonsense variants presented decreased stability. In contrast, the missense variants exhibited normal or increased stability but behaved as loss-of-function variants in yeast complementation and TDP-43 disaggregation assays. Our findings suggest that DNAJB4 is an emerging cause of myopathy with rigid spine syndrome of variable age of onset and severity. This diagnosis should be considered in individuals presenting with suggestive symptoms, particularly if they exhibit neck stiffness during infancy or experience respiratory failure in adults without significant limb muscle weakness. Missense variants in the J domain may predict a more severe phenotype.
Scaffolding-informed design of open educational resources in Chinese secondary school mathematics: insights from multi-cycle formative evaluation
Authors: Huang Xiaowei , Lo Chung Kwan , He Jiaju , Xu Simin , Kinshuk
Published: October 2024

In the post-pandemic world, open educational resources (OER) have the potential to ensure educational equity by providing all students with access to learning materials and by supporting teachers’ instructional practices through readily available, adaptable resources. However, the quality of OER continues to be a concern. Therefore, this study explored the use of (1) GeoGebra and scaffolding strategies to develop OER for secondary school mathematics teaching and (2) formative evaluation techniques to enhance the quality of the OER. A GeoGebra expert and a total of 40 frontline teachers participated in three review cycles of the OER development in the project. The feedback from each cycle informed the application of scaffolding strategies in the development of OER for the subsequent cycles. In Cycles 2 and 3, teachers rated the OER and provided feedback through surveys for further improvement. The results indicated that teacher ratings were significantly higher in Cycle 3 (n = 40, Mdn = 5) than in the previous cycle (n = 21, Mdn = 4) regarding the appropriateness of the OER for students with different learning preferences, z = − 2.87, p < 0.05. The results of the project-end satisfaction survey further revealed that all of the teacher participants were satisfied with the OER, which also enhanced their teaching practices. The results of the study offer a theoretical foundation that OER developers can ground upon to enhance their OER design. They also provide practical insights into the application of formative evaluation in the OER development that OER developers can adopt to create resources that are finely attuned to the needs of frontline teachers.
Decortication with uniport video-assisted thoracoscopic surgery for empyema due to postoperative esophageal leakage: a report of two pediatric cases
Authors: Goto Yudai , Ogata Seiya , Shimizu Hirofumi , Yamashita Michitoshi , Inoue Takuya , Hasegawa Takeo , Shio Yutaka , Suzuki Hiroyuki , Tanaka Hideaki
Published: October 2024

Background

Video-assisted thoracoscopic surgery (VATS) is considered useful for the treatment of parapneumonic empyema in children. However, thoracoscopic management of empyema due to esophageal leakage as an operative complication has not been well described in the literature.

Case presentation

We successfully decorticated severe empyema using uniport VATS in 2 children (a 2-year-old boy who suffered esophageal perforation after laparoscopic anti-reflux surgery, and a 7-month-old girl who had anastomotic leakage after thoracoscopic repair of esophageal atresia). In these patients, we noticed that pleural effusion rapidly progressed to empyema and caused respiratory insufficiency due to wide-range coverage by fibrotic pleural rind that was successfully decorticated under video-assisted vision from a mini-thoracotomy, followed by spontaneous healing of the leakage.

Conclusions

We did not attempt to closely approach or try to repair the esophageal leakage. We believe that this is an important tip for these situations.
Prevalence and severity of insomnia in adult outpatients attending Kasralainy Psychiatry and Addiction Treatment Hospital
Authors: Asal Abd El Rahman Ali , Abdalraheem Eman Abdalraheem Abdalbadeea , Saleh Alia Adel , Khalil Mohamed A. , Elnawawy Yassmin
Published: October 2024

Background

Insomnia is common among patients with psychiatric disorders and affects the clinical presentation and outcomes of the psychiatric disorder. The presentation of insomnia varies according to the type and severity of the psychiatric disorder.

Objectives

This cross-sectional study aimed to assess the prevalence and severity of insomnia in adult psychiatric outpatients attending Psychiatry and Addiction Medicine Hospital, Faculty of Medicine, Cairo University. The study included 390 patients diagnosed with the following disorders: depressive disorders (n = 126 (32.2%)), anxiety disorders (n = 69 (17.6%)), psychotic spectrum disorders (n = 67 (17.1%)), bipolar and related disorders (n = 50 (12.8%)), trauma and stress-related disorders (n = 46 (11.8%)), obsessive–compulsive disorder (n = 30 (7.7%)), and somatic symptoms disorders (n = 2 (0.5%)). Patients were assessed using the Sleep Disorder Interview, Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Index (ISI), and Global Assessment of Functioning Scale (GAF).

Results

Among the assessed patients, 314 (80.5%) had insomnia, with a higher prevalence in females (91.5%) compared to males (67.2%). The prevalence of insomnia was 96% in depressive disorders, 97.1% in anxiety disorders, 49.3% in psychotic disorders, and 32% in bipolar and related disorders; while all patients with trauma and stress-related disorders, obsessive–compulsive disorders, and somatic symptoms disorders had insomnia.

The severity of insomnia as measured by ISI was positively correlated with the global functioning score (r = 0.341, p =  < 0.001) and negatively correlated with the duration of the psychiatric illness (r =  − 0.285, p =  < 0.001).

Conclusions

Insomnia is highly prevalent in outpatients with psychiatric disorders.
Evidencing the challenges of care delivery for people with intellectual disability and epilepsy in England by using the Step Together toolkit
Authors: Shillito Tom , Watkins Lance , Ali Hafsha , Page Georgia , Pullen Angie , Mitchell Sarah , Roy Ashok , Sen Arjune , Kinney Michael , Thomas Rhys , Tittensor Phil , Bagary Manny , Subramanium Arun , Kent Bridie , Shankar Rohit
Published: October 2024

Background

People with intellectual disability (PwID) and epilepsy have increased premature and potentially preventable mortality. This is related to a lack of equitable access to appropriate care. The Step Together guidance and toolkit, developed with patient, clinical, charity and commissioning stakeholders, allows evaluation and benchmarking of essential epilepsy service provision for PwID in eight key domains, at a care system level.

Aims

To evaluate care provisions for adult PwID and epilepsy at a system level in the 11 integrated care systems (ICSs) of the Midlands, the largest NHS England region (population: approximately 11 million), using the Step Together toolkit

Method

Post training, each ICS undertook its benchmarking with the toolkit and submitted their scores to Epilepsy Action, a national UK epilepsy charity, who oversaw the process. The outcomes were analysed descriptively to provide results, individual and cumulative, at care domain and system levels.

Results

The toolkit was completed fully by nine of the 11 ICSs. Across all eight domains, overall score was 44.2% (mean 44.2%, median 43.3%, range 52.4%, interquartile range 23.8–76.2%). The domains of local planning (mean 31.1%, median 27.5%) and care planning (mean 31.4%, median 35.4%) scored the lowest, and sharing information scored the highest (mean 55.2%, median 62.5%). There was significant variability across each domain between the nine ICS. The user/carer participation domain had the widest variation across ICSs (0–100%).

Conclusions

The results demonstrate a significant variance in service provision for PwID and epilepsy across the nine ICSs. The toolkit identifies specific areas for improvement within each ICS and region.
Phase III Evaluation of Treatment Combinations in Three-Arm Trials
Authors: Korn Edward L. , Allegra Carmen J. , Freidlin Boris
Published: October 2024

Phase III trials that randomly assign patients to a control treatment (C), an experimental treatment (A), or a combination treatment (AB) should be designed with the goal to recommend the best treatment: AB (if it is better than A and C), A (if it is better than C, and AB is not better than A), or C (if neither AB nor A is better than C). However, this goal can be challenging to achieve with statistical confidence. We performed a survey of cancer trials published in five journals from January 2018 to May 2024 to assess the trial designs being used in this setting and found that three quarters of them did not have a provision for a formal comparison of the AB treatment arm with the A treatment arm, a possible shortcoming. A limited simulation evaluates two analysis strategies that incorporate an AB versus A comparison and is used to formulate some recommendations for designing these types of trials.
Stereotactic Radiosurgery Dose Reduction for Melanoma Brain Metastases Patients on Immunotherapy or Target Therapy: A Single-Center Experience
Authors: Tos Salem M. , Mantziaris Georgios , Shaaban Ahmed , Pikis Stylianos , Dumot Chloe , Sheehan Jason P.
Published: October 2024

BACKGROUND AND OBJECTIVES:

Better local control but higher rates of adverse radiation events (ARE) have been reported when combining American Society for Radiation Oncology (ASTRO)-guideline-suggested dose (SD) stereotactic radiosurgery (SRS) with immunotherapy or targeted therapy for melanoma brain metastases. The objective of this study is to explore the efficacy and safety of lower prescription doses compared with ASTRO guidelines for single-fraction SRS for patients with melanoma metastases who are concurrently receiving immunotherapy or targeted therapy.

METHODS:

We conducted a retrospective, single-center study on 194 patients who underwent SRS between 2009 and 2022. After propensity score matching, 71 patients with 292 metastases were included in the ASTRO-SD (20-24 Gy for <2 cm, 18 Gy for ≥2 to <3 cm) group and 33 patients with 292 metastases in the reduced dose (RD, <20 Gy for <2 cm, <18 Gy for ≥2 to <3 cm) group.

RESULTS:

The median diameter (5.4 vs 5.2 mm, P = .6), prescription volume (0.2 vs 0.2 cm3, P = .2), and radiographic follow-up (11 vs 12 months, P = .2) were similar in the 2 groups. The cumulative incidence of progressing metastases was significantly higher in the SD compared with the RD group (P = .018). Higher prescription volumes and ASTRO-suggested radiation doses were associated with local progression in multivariable analysis. Radiographic AREs were significantly more common in the SD compared with the RD group (8.6% vs 3.1%, P = .005). BRAF and other tyrosine kinase inhibitors’ concurrent use, higher prescription volumes, and ASTRO-suggested radiation doses were associated with an increased risk of radiographic ARE.

CONCLUSION:

This study provides evidence that RD SRS could offer reduced toxicity rates, while maintaining high local control as compared with the current guideline-SDs for the treatment of melanoma brain metastases.
Contrasting the development of larval and adult body plans during the evolution of biphasic lifecycles in sea urchins
Authors: McDonald Brennan D. , Massri Abdull J. , Berrio Alejandro , Byrne Maria , McClay David R. , Wray Gregory A.
Published: October 2024

Biphasic lifecycles are widespread among animals, but little is known about how the developmental transition between larvae and adults is regulated. Sea urchins are a unique system for studying this phenomenon because of the stark differences between their bilateral larval and pentaradial adult body plans. Here, we use single-cell RNA sequencing to analyze the development of Heliocidaris erythrogramma (He), a sea urchin species with an accelerated, non-feeding mode of larval development. The sequencing time course extends from embryogenesis to roughly a day before the onset of metamorphosis in He larvae, which is a period that has not been covered by previous datasets. We find that the non-feeding developmental strategy of He is associated with several changes in the specification of larval cell types compared to sea urchins with feeding larvae, such as the loss of a larva-specific skeletal cell population. Furthermore, the development of the larval and adult body plans in sea urchins may utilize largely different sets of regulatory genes. These findings lay the groundwork for extending existing developmental gene regulatory networks to cover additional stages of biphasic lifecycles.
The oligonucleotides containing N7-regioisomer of guanosine: influence on thermodynamic properties and structure of RNA duplexes
Authors: Jarmolowicz Aleksandra , Dutta Nivedita , Andralojc Witold , Sarzynska Joanna , Framski Grzegorz , Baranowski Daniel , Boryski Jerzy , Lahiri Ansuman , Gdaniec Zofia , Kierzek Elzbieta , Kierzek Ryszard
Published: October 2024

During the chemical synthesis of the purine riboside, N7-regioisomer is kinetically formed, whereas N9-regioisomer is a thermodynamically formed product. We have studied the effect of substituting N9-regioisomer of guanosine with its N7-regioisomer (N7-guanosine, 7G) at a central position of several RNA duplexes. We found that this single substitution by 7G severely diminished their thermodynamic stabilities when 7G paired with C and U, but remarkably, led to a significant amount of stabilization in most of the duplexes when forming mismatches with G and A. The extent of stabilization was observed to be dependent on the sequence and orientation of neighboring base pairs of N7-guanosine. 1D and 2D NMR studies on the duplexes along with extensive molecular dynamics simulations revealed the conformational differences occurring due to the substitution of G by 7G, and it was observed that the thermodynamic results were largely explainable by considering the formation of stable noncanonical hydrogen bonding interactions, although other interactions such as stacking and electrostatic interactions could also play a role. These observations can have important applications in the design of RNA-based disease diagnostics and therapeutics.
Viral interactions with host factors (TIM-1, TAM -receptors, Glut-1) are related to the disruption of glucose and ascorbate transport and homeostasis, causing the haemorrhagic manifestations of viral haemorrhagic fevers.
Authors: Chicano Wust Ivan
Published: October 2024

The haemorrhagic features of viral haemorrhagic fevers may be caused by common patterns of metabolic disturbances of the glucose and ascorbate homeostasis. Haemorrhages and vasculature disfunctions are a clinical feature not only of viral haemorrhagic fevers, but also in scurvy, diabetes and thrombotic microangiopathic haemolytic anaemia. Interestingly, the expression of glucose and ascorbate transporter Glut-1 on the erythrocyte membrane is associated with the inability to synthesize ascorbate and is restricted to that very species that are susceptible to filoviruses (primates, humans and fruit bats). Glut-1 may play a pivotal role in haemorrhagic fever pathogenesis. TIM-1 and TAM receptors have been recognized to enhance entry of Ebola, Lassa and Dengue viruses and viral interferences with TIM-1 could disturb its function, disturbing the expression of Glut-1. In those species not able to synthesize ascorbate and expressing Glut-1 on erythrocytes virus could interact with Glut-1 or other functionally related protein, and the influx of glucose into the cells would be severely impaired. As a consequence, transient hyperglycemia and a marked oxidative stress coupled with the high levels of glucose in plasma would be established, and then promote the activation of NF–κB transcription, exacerbating a pro-inflammatory response mediated by cytokines and chemokines: The inability to synthesize ascorbate is an Achilles Heel when trying to counteract the oxidative stress.
Does AI Think?
Authors: Crespo Ricardo
Published: October 2024

This article raises a very relevant question today: “Does AI think?” To come up with an answer, it explores several conceptions of knowledge, from classical Aristotelian notions to modern philosophers’ takes on it. For Aristotle, knowledge starts with the senses, and, through epagoge and nous, it grows into an understanding of the nature of the thing known, which is something that does not happen with AI. Modern schools of thoughts are either rationalist or empiricist. For rationalists, knowledge is innate, while empiricists believe all knowledge comes from the senses. As Kant views it, knowledge is “built” on sensorial data with the use of theoretical reason categories. Based on these approaches, it is harder to claim that AI does not think by itself. The article also reviews current philosophers’ views on AI and AI thinking. Summing up, the answer to the initial question depends on the concept of knowledge adopted. As this article shares the classical notion of thinking, it concludes that AI does not think.
Michael Heller’s Theology of Science in a Trinitarian Perspective: Ontological Aspects
Authors: Grygiel Wojciech Piotr , Kałuża Krystian
Published: October 2024

This paper explores the program of theology of science proposed by renowned Polish physicist and philosopher, Michael Heller, with a particular focus on its ontological dimensions through the lens of Trinitarian theology. Firstly, an overview of the status and current discussions of theology of science is presented. Next, drawing on Heller's key texts the Trinitarian doctrine is used to enhance the intelligibility of the Universe, wherein the dynamic interplay of unity, diversity, and relationality is mirrored in the structure of physical reality itself. Most importantly, however, we examine how Heller's theological perspective thus equipped provides justification for the specificity of the method of science itself, thereby revealing new dimensions of relations between science and theology. Through critical engagement with Heller's thought, this paper seeks ultimately to illuminate the profound implications of a Trinitarian perspective in his theology of science, shedding light on the interconnectedness of Christian doctrine and ontology in shaping our understanding of the universe and its underlying structure.
Polite Social Practices in 18th-century Scotland
Authors: Śliwa Marta
Published: October 2024

This article explores the role and influence of elite women in 18th-century Scotland, focusing on their engagement with polite social practices during the Scottish Enlightenment. The Scottish Enlightenment, characterized by its integration of various disciplines and emphasis on both theoretical and practical knowledge, was a period of significant cultural intellectual development. Central to this movement was the concept of politeness, which shaped the social interactions of the elite and played a crucial role in their personal and societal advancement. Elite women were integral to the social fabric of this era, participating in mixed-gender activities and shaping the cultural landscape through their involvement in social gatherings, education, and print culture. Despite being formally excluded from public office and direct political power, these women exercised significant influence through social networks, family ties, and patronage, subtly navigating the political and intellectual currents of their time. The study highlights how these women, while adhering to socially accepted norms, found ways to circumvent formal exclusions, thereby contributing to the broader cultural and political life of Scotland. Their participation in polite sociability not only facilitated their integration into elite society but also played a vital role in the broader program of social improvement that characterized the Scottish Enlightenment. This article underscores the complex interplay between gender, power, and politics, revealing how elite women helped shape “The Golden Age” of Scotland through their engagement in polite social practices.
Ontological and Axiological Foundations of the Meaning of Human Life in Nicolai Hartmann's Philosophy
Authors: Kopciuch Leszek
Published: October 2024

The subject of this article is Nicolai Hartmann's conception of the ontological and axiological foundations of the meaning of human life. Referring to both Hartmann's major and minor, I analyze his conception of human meaning in the dimension of individual life and in the historical dimension. I begin my discussion with a brief overview of Hartmann's relation to the earlier metaphysics of meaning. Then, I focus on identifying the ontological foundations of meaning. In this section, I specifically present Hartmann’s understanding of the laws of real being, his critique of ontological monism, and, of particular importance, his critique of teleological monism. I also reconstruct the most important elements of Hartmann’s conception of man as a spiritual being, comprising the personal spirit of the objective spirit and the objectified spirit. Another point of consideration is the question of the axiological basis of meaning. For Hartmann, humans construct their specific position in the world by introducing axiological criteria and axiological points of view into the real world. As Hartmann argues, man is the intermediary between ideal values and the real world. The final point of consideration is the problem of historical meaning.
Care home closures: what directors need to know about insolvency
Authors: Bernstein Adam
Published: October 2024

Adam Bernstein discusses what to do to avoid insolvency and closure of care homes.
Measurement of plasma characteristic parameters of copper foil explosion using interferometry
Authors: Li DangJuan , Lu Yuyan , Wang Jia , Guo Rongli , Wang Kexuan , Su Junhong , Wu ShenJiang
Published: October 2024

The accurate testing of plasma temperature and electron density and shock wave pressure during an electroburst in a copper foil transducer is critical for the characterization of the detonation performance of its elements. In this paper, the sequence of interferograms during the detonation of a copper foil transducer is captured at a frame rate of 3×106fps in conjunction with Mach–Zehnder interferometry and high-speed photography, and the results clearly demonstrate the propagation of the shock wave wavefront and plasma. The phase differences disturbed by plasma are extracted using the Fourier transform method, and the refractive index distributions are reconstructed with the Abel algorithm. Subsequently, based on the refractive index models of the shock wave and plasma, the shock wave pressure and plasma temperature and electron density are partitioned and reconstructed. Results show that the maximum shock wave pressure in the detonation of the copper foil transducer element is 1.297 atm, the maximum plasma temperature is 16,280 K, and the maximum plasma electron density is 2.134×1017cm−3. This study provides a theoretical and technical foundation for the detonation performance testing of pyrotechnic energy-conversion components.
Prediction of laser beam spatial profiles in a high-energy laser facility by use of deep learning
Authors: Guardalben M. J. , Goduguluri L. N. , Mathur A. , Wang J. , Yadav R.
Published: October 2024

We adapt the significant advances achieved recently in the field of generative artificial intelligence/machine-learning to laser performance modeling in multipass, high-energy laser systems with application to high-shot-rate facilities relevant to inertial fusion energy. Advantages of neural-network architectures include rapid prediction capability, data-driven processing, and the possibility to implement such architectures within future low-latency, low-power consumption photonic networks. Four models were investigated that differed in their generator loss functions and utilized the U-Net encoder/decoder architecture with either a reconstruction loss alone or combined with an adversarial network loss. We achieved inference times of 1.3 ms for a 256 × 256 pixel near-field beam with errors in predicted energy of the order of 1% over most of the energy range. It is shown that prediction errors are significantly reduced by ensemble averaging the models with different weight initializations. These results suggest that including the temporal dimension in such models may provide accurate, real-time spatiotemporal predictions of laser performance in high-shot-rate laser systems.
Quantum teleportation coexisting with classical communications in optical fiber
Authors: Thomas Jordan M. , Yeh Fei I. , Chen Jim Hao , Mambretti Joe J. , Kohlert Scott J. , Kanter Gregory S. , Kumar Prem
Published: October 2024

The ability for quantum and conventional networks to operate in the same optical fibers would aid the deployment of quantum network technology on a large scale. Quantum teleportation is a fundamental operation in quantum networking, but has yet to be demonstrated in fibers populated with high-power conventional optical signals. Here we report, to the best of our knowledge, the first demonstration of quantum teleportation over fibers carrying conventional telecommunications traffic. Quantum state transfer is achieved over a 30.2-km fiber carrying 400-Gbps C-band classical traffic with a Bell state measurement performed at the fiber’s midpoint. To protect quantum fidelity from spontaneous Raman scattering noise, we use optimal O-band quantum channels, narrow spectro-temporal filtering, and multi-photon coincidence detection. Fidelity is shown to be well maintained with an elevated C-band launch power of 18.7 dBm for the single-channel 400-Gbps signal, which we project could support multiple classical channels totaling many terabits/s aggregate data rates. These results show the feasibility of advanced quantum and classical network applications operating within a unified fiber infrastructure.
Monitoring of activity-driven trafficking of endogenous synaptic proteins through proximity labeling
Authors: Pascual-Caro Carlos , de Juan-Sanz Jaime
Published: October 2024

To enable transmission of information in the brain, synaptic vesicles fuse to presynaptic membranes, liberating their content and exposing transiently a myriad of vesicular transmembrane proteins. However, versatile methods for quantifying the synaptic translocation of endogenous proteins during neuronal activity remain unavailable, as the fast dynamics of synaptic vesicle cycling difficult specific isolation of trafficking proteins during such a transient surface exposure. Here, we developed a novel approach using synaptic cleft proximity labeling to capture and quantify activity-driven trafficking of endogenous synaptic proteins at the synapse. We show that accelerating cleft biotinylation times to match the fast dynamics of vesicle exocytosis allows capturing endogenous proteins transiently exposed at the synaptic surface during neural activity, enabling for the first time the study of the translocation of nearly every endogenous synaptic protein. As proof-of-concept, we further applied this technology to obtain direct evidence of the surface translocation of noncanonical trafficking proteins, such as ATG9A and NPTX1, which had been proposed to traffic during activity but for which direct proof had not yet been shown. The technological advancement presented here will facilitate future studies dissecting the molecular identity of proteins exocytosed at the synapse during activity, helping to define the molecular machinery that sustains neurotransmission in the mammalian brain.
Best practices for estimating and reporting epidemiological delay distributions of infectious diseases
Authors: Charniga Kelly , Park Sang Woo , Akhmetzhanov Andrei R. , Cori Anne , Dushoff Jonathan , Funk Sebastian , Gostic Katelyn M. , Linton Natalie M. , Lison Adrian , Overton Christopher E. , Pulliam Juliet R. C. , Ward Thomas , Cauchemez Simon , Abbott Sam
Published: October 2024

Epidemiological delays are key quantities that inform public health policy and clinical practice. They are used as inputs for mathematical and statistical models, which in turn can guide control strategies. In recent work, we found that censoring, right truncation, and dynamical bias were rarely addressed correctly when estimating delays and that these biases were large enough to have knock-on impacts across a large number of use cases. Here, we formulate a checklist of best practices for estimating and reporting epidemiological delays. We also provide a flowchart to guide practitioners based on their data. Our examples are focused on the incubation period and serial interval due to their importance in outbreak response and modeling, but our recommendations are applicable to other delays. The recommendations, which are based on the literature and our experience estimating epidemiological delay distributions during outbreak responses, can help improve the robustness and utility of reported estimates and provide guidance for the evaluation of estimates for downstream use in transmission models or other analyses.
Competitive plasticity to reduce the energetic costs of learning
Authors: van Rossum Mark C. W. , Pache Aaron
Published: October 2024

The brain is not only constrained by energy needed to fuel computation, but it is also constrained by energy needed to form memories. Experiments have shown that learning simple conditioning tasks which might require only a few synaptic updates, already carries a significant metabolic cost. Yet, learning a task like MNIST to 95% accuracy appears to require at least 108 synaptic updates. Therefore the brain has likely evolved to be able to learn using as little energy as possible. We explored the energy required for learning in feedforward neural networks. Based on a parsimonious energy model, we propose two plasticity restricting algorithms that save energy: 1) only modify synapses with large updates, and 2) restrict plasticity to subsets of synapses that form a path through the network. In biology networks are often much larger than the task requires, yet vanilla backprop prescribes to update all synapses. In particular in this case, large savings can be achieved while only incurring a slightly worse learning time. Thus competitively restricting plasticity helps to save metabolic energy associated to synaptic plasticity. The results might lead to a better understanding of biological plasticity and a better match between artificial and biological learning. Moreover, the algorithms might benefit hardware because also electronic memory storage is energetically costly.
Multi-omics analyses of Bacillus amyloliquefaciens treated mice infected with Schistosoma japonicum reveal dynamics change of intestinal microbiome and its associations with host metabolism
Authors: Chen Hao , Huang Shuaiqin , Yao Siqi , Wang Jingyan , Huang Jing , Yu Zheng
Published: October 2024

Background

Schistosomiasis japonica is a serious threat to human health. It causes damage to the intestine and liver. Probiotic therapy has been shown to be effective in alleviating intestinal diseases and improving host health. Previous studies have found that Bacillus amyloliquefaciens could alleviate the pathological symptoms of schistosomiasis japonica, but the regulatory mechanism of alleviating schistosomiasis japonica is still unknown.

Principal findings

This study analyzed the dynamic changes of intestinal microbiome in mice infected with Schistosoma japonicum after the intervention of B. amyloliquefaciens and its connection to host metabolism by multi-omics sequencing technology. B. amyloliquefaciens was found to significantly regulate the homeostasis of intestinal microbiota by promoting the growth of beneficial bacteria and inhibiting potential pathogenic bacteria and protect the number of core microbes. Meanwhile, the genes related to the metabolism of glycerophospholipids and amino acid from intestinal microbiome changed significantly, and were shown to be significantly positively correlated with the associated metabolites of microbial origin. Moreover, host metabolism (lipid metabolism and steroid hormone biosynthesis) was also found to be significantly regulated.

Conclusions

The recovery of intestinal microbial homeostasis and the regulation of host metabolism revealed the potential probiotic properties of B. amyloliquefaciens, which also provided new ideas for the prevention and adjuvant treatment of schistosomiasis japonica.
Intra-specific variations in Schistosoma mansoni and their possible contribution to inconsistent virulence and diverse clinical outcomes
Authors: Dannenhaus Tim A. , Winkelmann Franziska , Reinholdt Cindy , Bischofsberger Miriam , Dvořák Jan , Grevelding Christoph G. , Löbermann Micha , Reisinger Emil C. , Sombetzki Martina
Published: October 2024

Background

Schistosoma mansoni was introduced from Africa to the Americas during the transatlantic slave trade and remains a major public health problem in parts of South America and the Caribbean. This study presents a comprehensive comparative analysis of three S. mansoni strains with different geographical origins—from Liberia, Belo Horizonte and Puerto Rico. We demonstrated significant variation in virulence and host-parasite interactions.

Methods

We investigated the phenotypic characteristics of the parasite and its eggs, as well as the immunopathologic effects on laboratory mouse organ systems.

Results

Our results show significant differences in worm morphology, worm burden, egg size, and pathologic organ changes between these strains. The Puerto Rican strain showed the highest virulence, as evidenced by marked liver and spleen changes and advanced liver fibrosis indicated by increased collagen content. In contrast, the strains from Liberia and Belo Horizonte had a less pathogenic profile with less liver fibrosis. We found further variations in granuloma formation, cytokine expression and T-cell dynamics, indicating different immune responses.

Conclusion

Our study emphasizes the importance of considering intra-specific variations of S. mansoni for the development of targeted therapies and public health strategies. The different virulence patterns, host immune responses and organ pathologies observed in these strains provide important insights for future research and could inform region-specific interventions for schistosomiasis control.
Modeling spatiotemporal dynamics of Amblyomma americanum questing activity in the central Great Plains
Authors: Cobos Marlon E. , Winters Taylor , Martinez Ismari , Yao Yuan , Xiao Xiangming , Ghosh Anuradha , Sundstrom Kellee , Duncan Kathryn , Brennan Robert E. , Little Susan E. , Peterson A. Townsend
Published: October 2024

Ticks represent important vectors of a number of bacterial and viral disease agents, owing to their hematophagous nature and their questing behavior (the process in which they seek new hosts). Questing activity is notably seasonal with spatiotemporal dynamics that needs to be understood in detail as part of mediating and mitigating tick-borne disease risk. Models of the geography of tick questing activity developed to date, however, have ignored the temporal dimensions of that behavior; more fundamentally, they have often not considered the sampling underlying available occurrence data. Here, we have addressed these shortfalls for Amblyomma americanum, the most commonly encountered tick in the central Great Plains, via (1) detailed, longitudinal sampling to characterize the spatiotemporal dimensions of tick questing activity; (2) randomization tests to establish in which environmental dimensions a species is manifesting selective use; and (3) modeling methods that include both presence data and absence data, taking fullest advantage of the information available in the data resource. The outcome was a detailed picture of geographic and temporal variation in suitability for the species through the two-year course of this study. Such models that take full advantage of available information will be crucial in understanding the risk of tick-borne disease into the future.
Metabolic rates of different demographics in the sand fiddler crab Leptuca pugilator
Authors: Stancil Carter , Smith Nanette , Fletcher Laura S. , Anderson Lars , Griffen Blaine D.
Published: October 2024

Studies on animal energetics often focus on standardized metabolic rates to facilitate comparison across systems. Yet these standardized measurements often do not capture the realistic demographic and environmental variation that is common in natural settings. Rather, individuals included in these studies are often non-reproducing, uninjured, resting adults that have not recently eaten–far from a representative sample. We measured the respiratory rates of the sand fiddler crab Leptuca pugilator in air immediately after capture in the field, and compared rates between males, females of different reproductive states, and juveniles. As expected, we show that metabolic rates were influenced by body mass and activity level. We also show that being vitellogenic or gravid had only minor impacts on metabolic costs of females. Importantly, we demonstrate how considering demographics allows for the detection of phenomena that would otherwise go unnoticed. We found that field metabolic rates of L. pugilator in air are as much as an order of magnitude higher than previous standard metabolic rates measured on post-prandial, quiescent individuals. These higher rates may reflect a combination of high activity and active digestion, as fiddler crabs actively feed during low tide periods. Our results highlight the importance of considering differences in sex, life history stage, and reproductive state of organisms in fluctuating environments, such as intertidal habitats, when assessing energy expenditure.
Bearing defect detection based on the improved YOLOv5 algorithm
Authors: Li Kangning , Jiao Peigang , Ding Jiaming , DU Weibo
Published: October 2024

In the field of bearing defect detection, Aiming at the problem of low efficiency in manual inspection and prone to missed detections in scenarios with small target defects, and overlapping targets, an improved YOLOv5-based object detection method is proposed. Firstly, in terms of feature extraction, the C3 modules in the original backbone of YOLOv5 are replaced with the finer-grained Res2Block modules to improve the model’s feature extraction ability. Secondly, in terms of feature fusion, a Bidirectional Feature Pyramid Network (BiFPN) is added to the original neck of YOLOv5 to enhance the fusion ability of shallow graphic features and deep semantic features. Finally, the performance of the improved YOLOv5 algorithm is validated through ablation experiments and comparative experiments with other defect detection algorithms, including the Small_obj algorithm the existing method of adding a small target detection head for identifying small target defects. The experimental results demonstrate that the improved YOLOv5 algorithm exhibits high mAP and accuracy in bearing defect detection, enabling more precise identification the types of small target defects on bearings in complex scenarios with multiple coexisting defects and overlapping detection targets, thereby providing valuable reference for practical bearing defect detection.