bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficient test for deviation from Hardy–Weinberg equilibrium with known or ambiguous typing in highly polymorphic loci
Authors: Shkuri Or , Israeli Sapir , Tshuva Yuli , Maiers Martin , Louzoun Yoram
Published: September 2024

The Hardy–Weinberg equilibrium (HWE) assumption is essential to many population genetics models. Multiple tests were developed to test its applicability in observed genotypes. Current methods are divided into exact tests applicable to small populations and a small number of alleles, and approximate goodness-of-fit tests. Existing tests cannot handle ambiguous typing in multi-allelic loci. We here present a novel exact test Unambiguous Multi Allelic Test (UMAT) not limited to the number of alleles and population size, based on a perturbative approach around the current observations. We show its accuracy in the detection of deviation from HWE. We then propose an additional model to handle ambiguous typing using either sampling into UMAT or a goodness-of-fit test test with a variance estimate taking ambiguity into account, named Asymptotic Statistical Test with Ambiguity (ASTA). We show the accuracy of ASTA and the possibility of detecting the source of deviation from HWE. We apply these tests to the HLA loci to reproduce multiple previously reported deviations from HWE, and a large number of new ones.
Heterogeneous latent transfer learning in Gaussian graphical models
Authors: Wu Qiong , Wang Chi , Chen Yong
Published: September 2024

Gaussian graphical models (GGMs) are useful for understanding the complex relationships between biological entities. Transfer learning can improve the estimation of GGMs in a target dataset by incorporating relevant information from related source studies. However, biomedical research often involves intrinsic and latent heterogeneity within a study, such as heterogeneous subpopulations. This heterogeneity can make it difficult to identify informative source studies or lead to negative transfer if the source study is improperly used. To address this challenge, we developed a heterogeneous latent transfer learning (Latent-TL) approach that accounts for both within-sample and between-sample heterogeneity. The idea behind this approach is to “learn from the alike” by leveraging the similarities between source and target GGMs within each subpopulation. The Latent-TL algorithm simultaneously identifies common subpopulation structures among samples and facilitates the learning of target GGMs using source samples from the same subpopulation. Through extensive simulations and real data application, we have shown that the proposed method outperforms single-site learning and standard transfer learning that ignores the latent structures. We have also demonstrated the applicability of the proposed algorithm in characterizing gene co-expression networks in breast cancer patients, where the inferred genetic networks identified many biologically meaningful gene–gene interactions.
Anatomical and behavioural correlates of auditory perception in developmental dyslexia
Authors: Qi Ting , Mandelli Maria Luisa , Watson Pereira Christa L , Wellman Emma , Bogley Rian , Licata Abigail E , Miller Zachary A , Tee Boon Lead , de Leon Jessica , Chang Edward F , Oganian Yulia , Gorno-Tempini Maria Luisa
Published: September 2024

Developmental dyslexia is typically associated with difficulties in basic auditory processing and manipulating speech sounds. However, the neuroanatomical correlates of auditory difficulties in developmental dyslexia and their contribution to individual clinical phenotypes are still unknown. Recent intracranial electrocorticography findings associated processing of sound amplitude rises and speech sounds with posterior and middle superior temporal gyrus (STG), respectively. We hypothesize that regional STG anatomy will relate to specific auditory abilities in developmental dyslexia and that auditory processing abilities will relate to behavioral difficulties with speech and reading.

One hundred and ten children (78 developmental dyslexia, 32 typically developing, age 7–15 years) completed amplitude rise time and speech-in-noise discrimination tasks. They also underwent a battery of cognitive tests. Anatomical MRI scans were used to identify regions in which local cortical gyrification complexity correlated with auditory behaviour.

Behaviourally, amplitude rise time but not speech-in-noise performance was impaired in developmental dyslexia. Neurally, amplitude rise time and speech-in-noise performance correlated with gyrification in posterior and middle STG, respectively. Furthermore, amplitude rise time significantly contributed to reading impairments in developmental dyslexia, while speech in noise only explained variance in phonological awareness. Finally, amplitude rise time and speech-in-noise performance were not correlated, and each task was correlated with distinct neuropsychological measures, emphasizing their unique contributions to developmental dyslexia.

Overall, we provide a direct link between the neurodevelopment of the left STG and individual variability in auditory processing abilities in neurotypical and dyslexic populations
Gene therapy for cardiac diseases: methods, challenges, and future directions
Authors: Grisorio Luca , Bongianino Rossana , Gianeselli Matteo , Priori Silvia Giuliana
Published: September 2024

Gene therapy is advancing at an unprecedented pace, and the recent success of clinical trials reinforces optimism and trust among the scientific community. Recently, the cardiac gene therapy pipeline, which had progressed more slowly than in other fields, has begun to advance, overcoming biological and technical challenges, particularly in treating genetic heart pathologies. The primary rationale behind the focus on monogenic cardiac diseases is the well-defined molecular mechanisms driving their phenotypes, directly linked to the pathogenicity of single genetic mutations. This aspect makes these conditions a remarkable example of ‘genetically druggable’ diseases. Unfortunately, current treatments for these life-threatening disorders are few and often poorly effective, underscoring the need to develop therapies to modulate or correct their molecular substrates. In this review we examine the latest advancements in cardiac gene therapy, discussing the pros and cons of different molecular approaches and delivery vectors, with a focus on their therapeutic application in cardiac inherited diseases. Additionally, we highlight the key factors that may enhance clinical translation, drawing insights from previous trials and the current prospects of cardiac gene therapy.
Are We Opening Pandora’s Box? Clones, Human Spare Parts and International Law
Authors: Zannoni Diego
Published: September 2024

This article aims to verify whether human cloning is prohibited in international law and, if so, to what extent. In order to answer this question, it seeks to demonstrate that the complexity of the phenomenon and its concrete implications require a series of appropriate distinctions to be made. The article starts with an overview of the different positions adopted by the member states during the debate in the United Nations (UN) General Assembly, which led to the adoption of the UN Declaration on Human Cloning and continues with a focus on the European legal human cloning framework to verify whether it is more precise than the general international one. It demonstrates that reproductive cloning is prohibited both at the global level and in Europe, while therapeutic cloning so far remains within the limits of lawfulness.
Context matters: a sociocultural framework for materials development
Authors: Carabantes Luis
Published: September 2024

English language education is commonly seen by practitioners and researchers as an activity that should take into account the teachers and learners’ sociocultural realities. Reflecting this, in this article I argue for the use of Activity Theory as a sociocultural framework to promote the development of practitioners’ contextually relevant learning materials. Illustrating from my own EAP practice, I show how I used Activity Theory to overcome the limitations of the materials that were provided at a British university to teach multimodality to a group of international foundation students. Whilst making the case that materials development should reflect the sociocultural nature of teaching and learning, the article also argues that materials development knowledge and skills should be part of teachers’ core pedagogical repertoire.
Real-World Comparison of Effectiveness, Treatment Persistence, and Safety of First-Line Advanced Therapies at 1 Year for Ulcerative Proctitis
Authors: Dalal Rahul S , Clarke Lindsay M , Carlin Alex , Cabral Heidy , Allegretti Jessica R
Published: September 2024

Lay Summary

In this retrospective cohort study, vedolizumab was associated with higher odds of steroid-free clinical remission at 1 year compared to anti-TNF agents for bio-naïve patients with ulcerative proctitis.
Exploring home healthcare clinicians’ needs for using clinical decision support systems for early risk warning
Authors: Xu Zidu , Evans Lauren , Song Jiyoun , Chae Sena , Davoudi Anahita , Bowles Kathryn H , McDonald Margaret V , Topaz Maxim
Published: September 2024

Objectives

To explore home healthcare (HHC) clinicians’ needs for Clinical Decision Support Systems (CDSS) information delivery for early risk warning within HHC workflows.

Methods

Guided by the CDS “Five-Rights” framework, we conducted semi-structured interviews with multidisciplinary HHC clinicians from April 2023 to August 2023. We used deductive and inductive content analysis to investigate informants’ responses regarding CDSS information delivery.

Results

Interviews with thirteen HHC clinicians yielded 16 codes mapping to the CDS “Five-Rights” framework (right information, right person, right format, right channel, right time) and 11 codes for unintended consequences and training needs. Clinicians favored risk levels displayed in color-coded horizontal bars, concrete risk indicators in bullet points, and actionable instructions in the existing EHR system. They preferred non-intrusive risk alerts requiring mandatory confirmation. Clinicians anticipated risk information updates aligned with patient’s condition severity and their visit pace. Additionally, they requested training to understand the CDSS’s underlying logic, and raised concerns about information accuracy and data privacy.

Discussion

While recognizing CDSS’s value in enhancing early risk warning, clinicians highlighted concerns about increased workload, alert fatigue, and CDSS misuse. The top risk factors identified by machine learning algorithms, especially text features, can be ambiguous due to a lack of context. Future research should ensure that CDSS outputs align with clinical evidence and are explainable.

Conclusion

This study identified HHC clinicians’ expectations, preferences, adaptations, and unintended uses of CDSS for early risk warning. Our findings endorse operationalizing the CDS “Five-Rights” framework to optimize CDSS information delivery and integration into HHC workflows.
Three-dimensional evaluation of the responses of two species of flies (Diptera) to an indoor light trap
Authors: Joiner Jillian M , Branca Alyssa S , Banfield Michael G , Downs Christopher H , Muzio Gabriel M , Borden John H
Published: September 2024

We used the Photonic Fence Monitoring Device (PFMD) to evaluate orientation by Musca domestica L. (Diptera: Muscidae), and Calliphora vicina Robineau-Desvoidy (Diptera: Calliphoridae) to the Zevo Flying Insect Trap Model 3. The PFMD’s dual cameras record infrared light (IR) reflected from a wavelength-specific fabric; insects do not reflect IR at the same wavelength and are tracked in 3 dimensions as moving objects. The plug-in trap emits ultraviolet and blue light from behind an opaque shield; attracted insects enter the space between the shield and the wall and are trapped on a sticky cartridge facing the wall. An experiment (N = 10) with replicates of approximately 40, 1- to 7-day-old mixed-sex flies of each species was conducted in a 6.1 m3 arena. Prior to turning the trap on, the fly movement was not directed toward the trap on the back wall of the arena, regardless of whether the overhead light was on or off. When the overhead light was off, the mean first catch of both species occurred within 5 min after the trap was turned on, and 33.1% and 41.8% of M. domestica and C. vicina, respectively, were caught. House flies flew toward the trap, many approaching from below, while C. vicina apparently walked or flew outside the field of view of the PFMD until they appeared on the vertical reflective surface, and then walked toward the trap from all directions. Our results show that the Zevo Trap attracts and catches flies, and that the PFMD can be used to track flying and walking flies.
Feeding behavior, life-history traits, and settling preference of Aulacorthum solani (Hemiptera: Aphididae) on resistant and susceptible soybeans
Authors: Han Xue , Lei Jiahui , Zhang Yuhan , Jia Yulong , Wang Xiaoyun , Liu Jian , Tian Zhenqi
Published: September 2024

Foxglove aphid, Aulacorthum solani Kaltenbach (Hemiptera: Aphididae), is a major pest worldwide. It can infest various crops, including soybean, and reduce yields. The use of insect-resistant cultivars can effectively manage pests. Dowling is a soybean cultivar that can control Aphis glycines through antibiosis and antixenosis. In this study, we investigated the feeding behavior of A. solani using electropenetrography (EPG), and its life-history traits using an age-stage, two-sex life table, and its settling preferences on Dowling (resistant) and Heinong 51 (HN51, susceptible) soybean cultivars. The Dowling cultivar showed strong antibiosis against A. solani. Aphids feeding on Dowling exhibited significantly reduced survival, fecundity, and longevity, and increased nymph duration. Moreover, Dowling had negative impacts on the demographic parameters of the aphids. The number of A. solani individuals was significantly less on Dowling than on HN51, indicating the antixenotic effects of Dowling. As shown using EPG, the mechanical blocking wave (F) of A. solani was significantly longer after feeding on Dowling than after feeding on HN51, indicating that Dowling has a higher mechanical resistance. In conclusion, Dowling exhibited strong resistance to A. solani. These results are beneficial for integrated pest management in soybean fields and breeding programs.
Functional roles of nicotinic acetylcholine receptors in dinotefuran and flupyrimin toxicity and their sublethal effects on Sogatella furcifera (Hemiptera: Delphacidae)
Authors: Wu Ling , Li Yongqi , Ding Wenbing , He Hualiang , Gao Hongshuai , Gao Qiao , Li Youzhi , Qiu Lin
Published: September 2024

Sogatella furcifera (Horváth) (Hemiptera: Delphacidae), a serious rice pest, has developed significant resistance to a wide range of pesticides. Neonicotinoid insecticides are currently the primary choice for controlling S. furcifera, yet their impact on the species remains poorly understood. In this study, we investigated the binding sites of a conventional insecticide (dinotefuran) and a novel insecticide (flupyrimin), and evaluated their sublethal effects on S. furcifera. Our results revealed that the LC50 of dinotefuran and flupyrimin were 2.51 mg/L and 2.80 mg/L in third-instar S. furcifera, respectively. RNA interference (RNAi) knockdown of S. furcifera nicotinic acetylcholine receptor (nAChR) alpha2 subunit (Sfα2) and S. furcifera nAChR beta1 subunit (Sfβ1) significantly reduced the susceptibility to dinotefuran by 18.7% and 16.8%, respectively, but had no effect on flupyrimin. Reproduction of the F0 and F1 generations was significantly inhibited by the LC25 of both dinotefuran and flupyrimin. In the dinotefuran treatment at LC25, the intrinsic growth rate (r) and finite growth rate (λ) were reduced to 0.15 and 0.16 days, respectively; the mean generation time (T) increased to 27.77 days, and the relative fitness was only 0.76 compared to the control. Additionally, the relative fitness (Rf) of the flupyrimin-treated group was reduced to 0.93 and 0.86 times that of the control group. The population dynamics of S. furcifera are significantly affected by both dinotefuran and flupyrimin, making these insecticides valuable tools for integrated pest management and the rational use of insecticides.
Surface potential distribution of resist exposed by electron beam and the non-charging exposure conditions
Authors: Kotera Masatoshi , Kono Yoshinobu
Published: September 2024

In this study, we experimentally analyzed the charging phenomenon when an insulating resist film on a conductive layer formed on bulk glass is irradiated by electron beams (EBs). To quantify the charging potential induced, an electrostatic force microscope device was installed in the scanning electron microscope sample chamber, and potential distributions formed under various exposure conditions were obtained. Based on the results obtained, a model for charge accumulation within the sample, explaining positive and negative charging and their transitions, was developed. At an EB acceleration voltage of 30 kV, the following observations were made: ‘global charging’ could be avoided by applying −5 V to the sample. Regarding ‘local charging’ near the exposure area of the EB, at low exposure doses, emission of secondary electrons from the sample surface induced positive charging, while the accumulation of incident electrons within the sample induced negative charging. At exposure doses where the effects of both are balanced, the sample exhibited zero potential, revealing the appearance of the ‘first zero-cross exposure dose’. At higher exposure doses, the sample transitions from negative to positive as the exposure dose increases due to the electron-beam-induced conduction, resulting in the so-called second zero-cross exposure dose. The exposure dose dependence of the charging potential distribution at various acceleration voltages was obtained. In particular, we found that at an acceleration voltage of 0.6 kV, the sample surface is not charged even when exposed to small to very large doses of EBs.
Digital Bildung as semantic emplacement
Authors: Thomas Neal
Published: September 2024

Reading the significance of place as mediated through digital knowledge systems, this article expands recent debates around digital Bildung to include the semanticization of culture. The latter term refers to how data infrastructures correlate entities in their factuality in lived contexts, making them retrievable by digital devices and amenable to predictive inference by machines. Building on the analysis of others who characterize digital Bildung as the production of a semantic self-consciousness in learners, the article seeks to address the role of information systems technique in this production. It locates certain core intellectual justifications for the semantic mediation of culture in the philosophy of Charles Sanders Peirce. Ultimately diagnosing digital Bildung as enculturation to Peircean metaphysics, the article goes on to thematize certain conceptual limitations of our epistemic emplacement via digital systems. Relying on other philosophers to surface these limitations—Jürgen Habermas, James Williams, and Jean-Hugues Barthélémy—the article concludes more polemically by suggesting that defining digital Bildung on the basis of semantic self-consciousness as it is currently understood may exacerbate a crisis of sense in datafied societies.
Trigeminal neuralgia, demyelinating polyneuropathy, and central nervous system involvement in a patient with an SH3TC2 mutation
Authors: Giannakis Alexandros , Chamko Gkirai , Sarmas Ioannis , Pepe Georgia , Sidiropoulos Christos , Konitsiotis Spiridon
Published: September 2024

Background

Charcot-Marie-Tooth type 4C (CMT4C) is a slowly progressive, autosomal recessive, sensorimotor polyneuropathy characterized by demyelination and distinct clinical features, including cranial nerve involvement. CMT4C is associated with pathogenic mutations in the SH3TC2 gene.

Methods

A patient presenting with gait instability due to demyelinating polyneuropathy and refractory trigeminal neuralgia underwent comprehensive evaluation. Nerve conduction studies, magnetic resonance imaging (MRI) of the brain, cervical spine, and thoracic spine, lumbar puncture, and genetic test through next generation sequencing were performed.

Results

The genetic test found an Arg1109Stop mutation in the SH3TC2 gene, associated with demyelinating polyneuropathy and cranial neuropathy. Interestingly, brain MRI showed multiple, nonenhancing white matter hyperintensities. This is the first case of CMT4C associated with white matter lesions.

Conclusion

Any patient with slowly progressive peripheral nervous system symptoms and disproportionally abnormal nerve conduction study findings should be tested for an inherited polyneuropathy and brain imaging for screening of possible central nervous system involvement should be performed. Further investigation is needed to elucidate the pathogenetic basis of CMT4C and a possible association with white matter lesions.
Characteristics of the Integument of Phyllomedusa burmeisteri (Anura, Phyllomedusidae) and Boana semilineata (Anura, Hylidae) Males Can Contribute to Understanding its Relation to Habitat
Authors: Valente Teixeira Stéphanie Asséf Millen , Moraes de Castro Mariana , Novaes Camila Moura , Marques dos Santos Daiane Cristina , da Penha Neves Charlene , Guimarães-Ervilha Luiz Otávio , Feio Renato Neves , Machado-Neves Mariana
Published: September 2024

The integument of anurans plays vital physiological roles, crucial for understanding the species' survival in their environment. Despite its significance, there are few studies describing the cutaneous morphology of anurans from the Brazilian Atlantic Forest. This study aimed to characterize the integument of Phyllomedusa burmeisteri and Boana semilineata in males using microscopic and histochemical approaches. Histological sections were stained with various dyes, and additional fragments underwent electron microscopy and energy-dispersive X-ray spectroscopy. Results showed different projections on the dorsal and ventral regions of males from these species, without the Eberth–Katschenko layer. Differences in the arrangement of chromatophore cells in regions with varying solar incidence were observed in the spongy dermis. Various gland types were identified, aiding taxonomic differentiation and validation of behavioral data. Both species had seromucous and granular glands, while only P. burmeisteri displayed lipid glands. Histochemical analysis revealed higher production of polysaccharides and proteins, contributing to the integument's moisture and protection. Lipid secretions in P. burmeisteri helped waterproof the integument more effectively against desiccation. This study concludes that analyzing anuran integument provides valuable insights into their behavior, with integument composition potentially influenced by habitat choice among different species.
Informational Capitalism as Phase Shift
Authors: Cohen Julie E.
Published: September 2024

In capitalist political economies, the emergence of informational and informationally mediated modes of development has produced important changes in the organization of economic and social activity that are best understood via a chemical analogy: as a phase shift in the nature and structure of interactions that dramatically alters systemic behaviour. This chapter first sketches two interlinked sets of changes that are central to the phase shift to informational capitalism: the data-driven, multi-dimensional commodification of economic and social resources and the pervasive embedding of economic and social relations in digital platforms. It then sketches a preliminary account of the implications of the phase shift for theories of digital constitutionalism.
Digital Bills of Rights
Authors: Celeste Edoardo , Iglesias Keller Clara , Redeker Dennis
Published: September 2024

The past two decades have witnessed the emergence of a significant number of documents that adopt a constitutional ‘tone’ in order to articulate rights and principles for the digital society. These ‘digital bills of rights’ have been drafted by a multitude of actors, often stemming from civil society initiatives and therefore lacking legally binding force. The chapter investigates to what extent these documents contribute to the project and ambitions of digital constitutionalism. It positions this phenomenon from a theoretical perspective and it considers their different degrees of institutionalization, analysing a series of concrete examples. Brazil is used as a case study to illustrate how digital bills of rights’ language can ultimately be embraced by state institutionalized processes, with direct consequences to public policy and jurisprudence.
The End of the Deception?
Authors: Botelho Catarina Santos
Published: September 2024

This chapter offers normative and philosophical arguments against an approach to automation that fully skips human agency and ethical accountability. It addresses the connection between the EU concepts of direct and indirect discrimination and the US concepts of disparate discrimination and disparate impact. It then focuses on understanding discriminatory algorithms and the illusion of algorithmic objectivity. These incursions lead, third, to the puzzling topic of regulating and debiasing algorithms. Fourth, building on the assertion that algorithms are not designed for straightforward human understanding, the chapter describes how to cope with algorithmic discrimination. Seen as a whole, there are bad news and good news regarding the brave new algorithmic world. The bad news is that algorithms are partially human and therefore never fully immune to biases and to the greed of pursuing innovation at any cost. The good news is that we are aware of algorithmic discrimination. To counter this, international, regional, and domestic digital constitutionalism, as well as administrative law, can guide algorithmic decision-making and governance.
Colour changes in the feet: a sign of autonomic symptoms in systemic sclerosis
Authors: Adler Brittany L , Kuchinad Kamini , Jeong Seeun Judy , Stiles Lauren E , Shah Ami A , Chung Tae , McMahan Zsuzsanna H
Published: September 2024

Objectives

Patients with autonomic dysfunction, or dysautonomia, often report discolouration of their dependent extremities, which is thought to be from venous pooling or acrocyanosis. A subset of patients with SSc are affected by dysautonomia but may be challenging to identify. We sought to determine whether patients with SSc who report discolouration in their feet have a higher burden of autonomic symptoms, including orthostatic, gastrointestinal (GI), urinary, secretomotor and pupillomotor.

Methods

167 patients with SSc completed the Composite Autonomic Symptom Score (COMPASS)-31 survey, which queries whether the patient experiences discolouration of the feet or hands. We compared the COMPASS-31 subdomain scores between SSc patients with and without foot discolouration. Seventy-nine patients with postural orthostatic tachycardia syndrome (POTS) also completed the COMPASS-31 questionnaire for comparison.

Results

We found that extremity discolouration is common in POTS and more often affects the feet, whereas in SSc, the hands are more frequently involved; 62% of SSc patients report colour changes in their feet. These patients are more likely to have other autonomic symptoms, including orthostatic (11.7 ± 10.6 vs 8.6 ± 9.9, P = 0.06), GI (11.3 ± 4.3 vs 8.8 ± 4.3, P = 0.0003), urinary (1.4 ± 1.5 vs 0.8 ± 1.3, P = 0.002) and secretomotor (7.0 ± 3.8 vs 5.9 ± 3.8, P = 0.06) symptoms. These associations persist in a multivariable model after adjusting for potential confounders.

Conclusion

Dependent extremity discolouration is common in dysautonomia. Patients with SSc who report colour changes in their feet are more likely to report other symptoms of autonomic dysfunction.
Progesterone Concentrations on Blastocyst Transfer Day in Modified Natural Cycle Frozen Embryo Transfer Cycles
Authors: Saupstad Marte , Bergenheim Sara J. , Bogstad Jeanette W. , Petersen Morten R. , Klajnbard Anna , Prætorius Lisbeth , Freiesleben Nina L. C. , Englund Anne L. , Løkkegaard Ellen C. L. , Knudsen Ulla B. , Husth Merete , Alsbjerg Birgit , Møller Julie E. , Dam Tine V. , Forman Julie L. , Pinborg Anja , Løssl Kristine
Published: September 2024

(Abstracted from Reprod Biomed Online 2024;49(1):article 103862)

With advances in in vitro fertilization (IVF) techniques, it has become safe and efficient to vitrify and warm embryos, and frozen embryo transfer (FET) now has comparable outcomes compared with fresh embryo transfer. A common approach to endometrial preparation for FET is hormone replacement therapy, and because women do not develop a corpus luteum when undergoing hormone replacement therapy–FET, finding an optimal concentration of progesterone is of great clinical interest.
Exercise-induced bronchoconstriction
Authors: Pruitt Bill , Gregory Karen L. , Cochran Audra
Published: September 2024

Exercise-induced bronchospasm (EIB) is a problem encountered by many people, and although it can be controlled, it is often overlooked or attributed to deconditioning. Children and elite athletes tend to have an increased incidence of EIB, but this condition is also encountered in others. Unfortunately, many who must deal with this disease tend to limit the level of exercise that provokes symptoms or avoid exercise altogether. EIB can occur alone or in association with underlying asthma. This article discusses EIB, its management, and strategies for nurses when caring for patients with EIB.
Age-related macular degeneration
Authors: James Lucretia Marie
Published: September 2024

Age-related macular degeneration (AMD) is the leading cause of visual impairment in patients age 50 and older, with an estimated 200 million people affected worldwide and a projected 288 million by 2040. This article provides an overview of the epidemiology, risk factors, pathophysiology, clinical manifestations, diagnosis, management, and nursing considerations for AMD to equip nurses with the knowledge to play a crucial role in the early detection of this disease.
A Decision Aid to Support Tubal Sterilization Decision-Making Among Pregnant Women: The MyDecision/MiDecisión Randomized Clinical Trial
Authors: Borrero Sonya , Mosley Elizabeth A. , Wu Michaella , Dehlendorf Christine , Wright Catherine , Abebe Kaleab Z. , Zite Nikki
Published: September 2024

(Abstracted from JAMA Network Open 2024;7:e242215)

Tubal sterilization is the most common contraceptive method among adult women in the United States. According to preliminary data, demand for this permanent contraception has risen since the US Supreme Court reduced access to abortions in 2022.
Screening activity of brain cancer-derived factors on primary human brain pericytes
Authors: McCullough Samuel JC , Albers Eliene , Anchan Akshata , Yu Jane , Connor Bronwen , Graham E. Scott
Published: September 2024

Brain cancers offer poor prognoses to patients accompanied by symptoms that drastically impact the patient and their family. Brain tumours recruit local non-transformed cells to provide trophic support and immunosuppression within the tumour microenvironment, supporting tumour progression. Given the localization and supportive role of pericytes at the brain vasculature, we explored the potential for brain pericytes to contribute to the brain cancer microenvironment. To investigate this, primary brain pericytes were treated with factors commonly upregulated in brain cancers. Changes to brain pericyte cell signalling, inflammatory secretion, and phagocytosis were investigated. The TGFβ superfamily cytokines TGFβ and GDF-15 activated SMAD2/3 and inhibited C/EBP-δ, revealing a potential mechanism behind the pleiotropic action of TGFβ on brain pericytes. IL-17 induced secretion of IL-6 without activating NFκB, STAT1, SMAD2/3, or C/EBP-δ signalling pathways. IL-27 and IFNγ induced STAT1 signalling and significantly reduced pericyte phagocytosis. The remaining brain cancer-derived factors did not induce a measured response, indicating that these factors may act on other cell types or require co-stimulation with other factors to produce significant effects. Together, these findings show potential mechanisms by which brain pericytes contribute to aspects of inflammation and starts to uncover the supportive role brain pericytes may play in brain cancers.
Modeling suggests SARS-CoV-2 rebound after nirmatrelvir-ritonavir treatment is driven by target cell preservation coupled with incomplete viral clearance
Authors: Phan Tin , Ribeiro Ruy M. , Edelstein Gregory E. , Boucau Julie , Uddin Rockib , Marino Caitlin , Liew May Y. , Barry Mamadou , Choudhary Manish C. , Tien Dessie , Su Karry , Reynolds Zahra , Li Yijia , Sagar Shruti , Vyas Tammy D. , Kawano Yumeko , Sparks Jeffrey A. , Hammond Sarah P. , Wallace Zachary , Vyas Jatin M. , Li Jonathan Z. , Siedner Mark J. , Barczak Amy K. , Lemieux Jacob E. , Perelson Alan S.
Published: September 2024

In a subset of SARS-CoV-2 infected individuals treated with the oral antiviral nirmatrelvir-ritonavir, the virus rebounds following treatment. The mechanisms driving this rebound are not well understood. We used a mathematical model to describe the longitudinal viral load dynamics of 51 individuals treated with nirmatrelvir-ritonavir, 20 of whom rebounded. Target cell preservation, either by a robust innate immune response or initiation of nirmatrelvir-ritonavir near the time of symptom onset, coupled with incomplete viral clearance, appear to be the main factors leading to viral rebound. Moreover, the occurrence of viral rebound is likely influenced by time of treatment initiation relative to the progression of the infection, with earlier treatments leading to a higher chance of rebound. Finally, our model demonstrates that extending the course of nirmatrelvir-ritonavir treatment, in particular to a 10-day regimen, may greatly diminish the risk for rebound in people with mild-to-moderate COVID-19 and who are at high risk of progression to severe disease. Altogether, our results suggest that in some individuals, a standard 5-day course of nirmatrelvir-ritonavir starting around the time of symptom onset may not completely eliminate the virus. Thus, after treatment ends, the virus can rebound if an effective adaptive immune response has not fully developed. These findings on the role of target cell preservation and incomplete viral clearance also offer a possible explanation for viral rebounds following other antiviral treatments for SARS-CoV-2.

Importance

Nirmatrelvir-ritonavir is an effective treatment for SARS-CoV-2. In a subset of individuals treated with nirmatrelvir-ritonavir, the initial reduction in viral load is followed by viral rebound once treatment is stopped. We show the timing of treatment initiation with nirmatrelvir-ritonavir may influence the risk of viral rebound. Nirmatrelvir-ritonavir stops viral growth and preserves target cells but may not lead to full clearance of the virus. Thus, once treatment ends, if an effective adaptive immune response has not adequately developed, the remaining virus can lead to rebound. Our results provide insights into the mechanisms of rebound and can help develop better treatment strategies to minimize this possibility.
Beyond Algorithms: The Impact of Simplified CNN Models and Multifactorial Influences on Radiological Image Analysis
Authors: Mohammadi Saber , Mohanty Abhinita S. , Saikali Shady , Rose Doori , LynnHtaik WintPyae , Greaves Raecine , Lounes Tassadit , Haque Eshaan , Hirani Aashi , Zahiri Javad , Dehzangi Iman , Patel Vipul , Khosravi Pegah
Published: September 2024

This paper demonstrates that simplified Convolutional Neural Network (CNN) models can outperform traditional complex architectures, such as VGG-16, in the analysis of radiological images, particularly in datasets with fewer samples. We introduce two adopted CNN architectures, LightCnnRad and DepthNet, designed to optimize computational efficiency while maintaining high performance. These models were applied to nine radiological image datasets, both public and in-house, including MRI, CT, X-ray, and Ultrasound, to evaluate their robustness and generalizability. Our results show that these models achieve competitive accuracy with lower computational costs and resource requirements. This finding underscores the potential of streamlined models in clinical settings, offering an effective and efficient alternative for radiological image analysis. The implications for medical diagnostics are significant, suggesting that simpler, more efficient algorithms can deliver better performance, challenging the prevailing reliance on transfer learning and complex models. The complete codebase and detailed architecture of the LightCnnRad and DepthNet, along with step-by-step instructions, are accessible in our GitHub repository athttps://github.com/PKhosravi-CityTech/LightCNNRad-DepthNet.
Few-shot Algorithms for Consistent Neural Decoding (FALCON) Benchmark
Authors: Karpowicz Brianna M. , Ye Joel , Fan Chaofei , Tostado-Marcos Pablo , Rizzoglio Fabio , Washington Clay , Scodeler Thiago , de Lucena Diogo , Nason-Tomaszewski Samuel R. , Mender Matthew J. , Ma Xuan , Arneodo Ezequiel Matias , Hochberg Leigh R. , Chestek Cynthia A. , Henderson Jaimie M. , Gentner Timothy Q. , Gilja Vikash , Miller Lee E. , Rouse Adam G. , Gaunt Robert A. , Collinger Jennifer L. , Pandarinath Chethan
Published: September 2024

Intracortical brain-computer interfaces (iBCIs) can restore movement and communication abilities to individuals with paralysis by decoding their intended behavior from neural activity recorded with an implanted device. While this activity yields high-performance decoding over short timescales, neural data are often nonstationary, which can lead to decoder failure if not accounted for. To maintain performance, users must frequently recalibrate decoders, which requires the arduous collection of new neural and behavioral data. Aiming to reduce this burden, several approaches have been developed that either limit recalibration data requirements (few-shot approaches) or eliminate explicit recalibration entirely (zero-shot approaches). However, progress is limited by a lack of standardized datasets and comparison metrics, causing methods to be compared in an ad hoc manner. Here we introduce the FALCON benchmark suite (Few-shot Algorithms for COnsistent Neural decoding) to standardize evaluation of iBCI robustness. FALCON curates five datasets of neural and behavioral data that span movement and communication tasks to focus on behaviors of interest to modern-day iBCIs. Each dataset includes calibration data, optional few-shot recalibration data, and private evaluation data. We implement a flexible evaluation platform which only requires user-submitted code to return behavioral predictions on unseen data. We also seed the benchmark by applying baseline methods spanning several classes of possible approaches. FALCON aims to provide rigorous selection criteria for robust iBCI decoders, easing their translation to real-world devices.https://snel-repo.github.io/falcon/
Exploring Differences in Functional Connectivity in Australian Rules Football Players : A Resting-State fMRI Study on the Default Mode Network
Authors: Tran Mi , Shrikumar Avanti , Hellewell Sarah C , Welton Thomas , Kirkby Max , Maller Jerome J , Smith Paul , Pearce Alan , Grieve Stuart M
Published: September 2024

The effects of non-concussive impacts in contact-sports such as in Australian rules football (ARF) are still largely unexplored. These impacts are often but not always lower in intensity, but occur more frequently than actual concussions. Since non-concussive impacts are often asymptomatic, their significance may be underestimated. Acute or subacute measurement of non-concussive injury is challenging as the pathological response and injury is poorly described. There is therefore a need for a greater understanding of the pathological consequences of exposure. Growing evidence indicates that resting-state functional connectivity (rs-fMRI) changes in the Default Mode Network (DMN) may be an important biomarker that is sensitive to characterize these impacts. In this work, we examined functional connectivity changes within the DMN of ARF players to evaluate its potential as an early biomarker for non-concussive impacts. Based on rs-fMRI, we compare the DMN of 47 sub-elite ARF players (mean age 21.5±2.7 years [SD], males 57%) and 42 age-matched healthy controls (mean age 23.2±2.3 years [SD], males 48%) using Independent Component Analysis (ICA) and Dual Regression. This approach permits an unbiased decomposition of brain activity into networks with principled handling of statistical error. An 83% increase in DMN connectivity (as measured by the Strictly Standardized Mean Difference on values derived from Dual Regression) was observed in ARF players in the left retrosplenial cingulate cortex compared to healthy controls (FDR-corrected p-value from dual regression = 0.03, 95% CI computed via bootstrapping was 58% to 116%). The AUC for distinguishing ARF players from controls was 0.80 (95% CI; [0.71, 0.89]), equating to a PPV of 78% and a NPV of 74%. These results are preliminary; future work could investigate robustness to different random initializations of ICA and validate the findings on an independent testing set, as well as investigate longitudinal changes in ARF players over the course of a playing season.
Filamentation activates bacterial NLR-like antiviral protein
Authors: Wang Yiqun , Tian Yuqing , Yang Xu , Yu Feng , Zheng Jianting
Published: September 2024

Bacterial antiviral STANDs (Avs) are evolutionarily related to the nucleotide-binding leucine-rich repeat containing receptors (NLRs) widely distributed in immune systems across animals and plants.EfAvs5, an Avs type 5 protein fromEscherichia fergusonii, contains an N-terminal SIR2 effector domain, a nucleotide-binding oligomerization domain (NOD) and a C-terminal sensor domain, conferring protection against diverse phage invasions. Despite the established roles of SIR2 and STAND in prokaryotic and eukaryotic immunity, the mechanism underlying their collaboration remains unclear. Here we present cryo-EM structures ofEfAvs5 filaments, elucidating the mechanisms of dimerization, filamentation, filament clustering, ATP binding and NAD+hydrolysis, all of which are crucial for anti-phage defense. The SIR2 domains and NODs engage in the intra- and inter-dimer interaction to form an individual filament, while the outward C-terminal domains contribute to bundle formation. Filamentation potentially stabilizes the dimeric SIR2 configuration, thereby activating the NADase activity ofEfAvs5.EfAvs5 is deficient in the ATPase activity, but elevated ATP concentrations can impede its NADase activity. Together, we uncover the filament assembly of Avs5 as a unique mechanism to switch enzyme activities and perform anti-phage defenses, emphasizing the conserved role of filamentation in immune signaling across diverse life forms.

Keypoints

EfAvs5 depletes NAD+for anti-phage defense.

EfAvs5 assembles as bundled filaments that can hydrolyze NAD+.

The SIR2 domain and NOD collaborate to form an individual filament.

The building block of the filament isEfAvs5 dimer.

The activity of theEfAvs5 complex is regulated by ATP.
Genetic-Dependent Brain Signatures of Resilience: Interactions among Childhood Abuse, Genetic Risks and Brain Function
Authors: Lu Han , Rolls Edmund T. , Liu Hanjia , Stein Dan J. , Sahakian Barbara J. , Elliott Rebecca , Jia Tianye , Xie Chao , Xiang Shitong , Wang Nan , Banaschewski Tobias , Bokde Arun L.W. , Desrivières Sylvane , Flor Herta , Grigis Antoine , Garavan Hugh , Heinz Andreas , Brühl Rüdiger , Martinot Jean-Luc , Martinot Marie-Laure Paillère , Artiges Eric , Nees Frauke , Orfanos Dimitri Papadopoulos , Lemaitre Herve , Poustka Luise , Hohmann Sarah , Holz Nathalie , Fröhner Juliane H. , Smolka Michael N. , Vaidya Nilakshi , Walter Henrik , Whelan Robert , Schumann Gunter , Feng Jianfeng , Luo Qiang ,   the IMAGEN Consortium
Published: September 2024

Resilience to emotional disorders is critical for adolescent mental health, especially following childhood abuse. Yet, brain signatures of resilience remain undetermined due to the differential susceptibility of the brain’s emotion processing system to environmental stresses. Analyzing brain’s responses to angry faces in a longitudinally large-scale adolescent cohort (IMAGEN), we identified two functional networks related to the orbitofrontal and occipital regions as candidate brain signatures of resilience. In girls, but not boys, higher activation in the orbitofrontal-related network was associated with fewer emotional symptoms following childhood abuse, but only when the polygenic burden for depression was high. This finding defined a genetic-dependent brain (GDB) signature of resilience. Notably, this GDB signature predicted subsequent emotional disorders in late adolescence, extending into early adulthood and generalizable to another independent prospective cohort (ABCD). Our findings underscore the genetic modulation of resilience-brain connections, laying the foundation for enhancing adolescent mental health through resilience promotion.
Probing the role of synaptic adhesion molecule RTN4RL2 in setting up cochlear connectivity
Authors: Karagulyan Nare , Überegger Maja , Qi Yumeng , Babai Norbert , Hofer Florian , Johnson Chacko Lejo , Wang Fangfang , Luque Maria , Glueckert Rudolf , Schrott-Fischer Anneliese , Hua Yunfeng , Moser Tobias , Bandtlow Christine
Published: September 2024

Sound encoding depends on the precise and reliable neurotransmission at the afferent synapses between the sensory inner hair cells (IHCs) and spiral ganglion neurons (SGNs). The molecular mechanisms contributing to the formation, as well as interplay between the pre- and postsynaptic components remain largely unclear. Here, we tested the role of the synaptic adhesion molecule and Nogo/RTN4 receptor homolog RTN4RL2 (also referred to as NgR2) in the development and function of afferent IHC-SGN synapses. Upon deletion of RTN4RL2 in mice (RTN4RL2-/-), presynaptic IHC active zones showed enlarged synaptic ribbons and a depolarized shift in the activation of CaV1.3 Ca2+channels. The postsynaptic densities (PSDs) of SGNs were smaller and deficient of GluA2/3 despite maintained Gria2 mRNA expression in SGNs. Next to synaptically engaged PSDs we observed “orphan” PSDs located away from IHCs. They likely belong to a subset of SGN peripheral neurites that do not contact the IHCs in RTN4RL2-/-cochleae as found by volume electron microscopy reconstruction of SGN neurites. Auditory brainstem responses of RTN4RL2-/-mice showed increased sound thresholds indicating impaired hearing. Together, these findings suggest that RTN4RL2 contributes to the proper formation and function of auditory afferent synapses and is critical for normal hearing.