Search

Abstract Hormone receptor-positive/HER2-negative breast cancer (BC) is the most common subtype of BC and typically occurs as an early, operable disease. In patients receiving neoadjuvant chemotherapy (NACT), pathological complete response (pCR) is rare and multiple efforts have been made to predict disease recurrence. We developed a framework to predict pCR using clinicopathological characteristics widely available at diagnosis. The machine learning (ML) models were trained to predict pCR (n = 463), evaluated in an internal validation cohort (n = 109) and validated in an external validation cohort (n = 151). The best model was an Elastic Net, which achieved an area under the curve (AUC) of respectively 0.86 and 0.81. Our results highlight how simpler models using few input variables can be as valuable as more complex ML architectures. Our model is freely available and can be used to enhance the stratification of BC patients receiving NACT, providing a framework for the development of risk-adapted clinical trials.

Abstract Neuronal ceroid lipofuscinoses (NCLs) are genetically heterogeneous neurodegenerative disorders, characterized by progressive cognitive and motor decline, epilepsy, visual impairment, and shortened life‐expectancy. CLN6‐related NCLs include both late‐infantile and adult myoclonic form. We report a 21‐year‐old patient, with mild developmental delay, who developed occipital seizures at 14 years, and subsequently cognitive decline, cortical myoclonus, and photosensitivity at low and higher frequencies. Overall, the picture suited progressive myoclonus epilepsy. Electroretinogram was normal. A skin biopsy revealed a mixed storage of curvilinear and fingerprint profiles. A brain MRI showed severe cortical atrophy. Performing genetic analyses, two biallelic variants were identified in the CLN6 gene, each inherited from one of the healthy parents, one c.722T>C, p.(Met241Thr) already described in the late‐infantile form and the other one c.486+28T>C, intronic and novel, causing aberrant splicing. In the patient, the expression of the allele containing c.722T>C variant was increased, in comparison with the carrier parent. The peculiar genetic pattern observed in the patient could explain a milder clinical picture when compared with late‐infantile form, since CLN6 expression was partially preserved. However, the presence of a delay, and the early cognitive decline suggested a continuum phenotype connecting late‐infantile and adult CLN6‐related forms. Plain Language Summary We report a patient with CLN6 disease who developed symptoms at an intermediate age: 9 years for mild intellectual disability and 14 years for occipital seizures and progressive myoclonus epilepsy, without visual impairment. The patient is compound heterozygous for a CLN6 missense variant c.722T>C, p.(Met241Thr) already described in the late‐infantile form and for a novel intronic variant c.486+28T>C, causing aberrant splicing. In the patient, the expression of the allele containing c.722T>C variant was increased, compared with the carrier parent. The splice site variant had a milder effect. The peculiar genetic pattern may explain the continuum phenotype between late‐infantile and adult forms.

Introduction: The relationship between obstructive sleep apnea (OSA) and cancer has been recognized for some time now. However, little is known about the mechanisms by which sleep apnea promotes tumorigenesis and the impact of OSA on survival after cancer diagnosis. In the last few years, research has focused on the exploration of different biomarkers to understand the mechanisms underlying this relationship and miRNAs, non-coding single strands of about 22 nucleotides that post-transcriptionally regulate gene expression, have emerged as possible actors of this process.The aim of the study was to evaluate the impact of OSA on survival of metastatic colorectal cancer (mCRC) patients based on the expression of specific miRNAs. Methods: The expression of 6 miRNAs, respectively miR-21, miR-23b, miR-26a, miR-27b, miR-145 and miR-210, was analyzed by qRT-PCR in patients’ sera. Response to first-line therapy, Kaplan-Meier curves of overall and progression-free survival were used to evaluate survival in mCRC patients with and without OSA stratified for the expression of miRNAs. Results: The expression of miR-21, miR-23b, miR-26a and miR-210 was significantly upregulated in mCRCs with OSA compared to no OSA. In mCRC patients with OSA and increasing expression of miR-21, miR-23b, miR-26a and miR-210 risk of progression after first-line therapy was higher and both overall and progression-free survival were significantly worst. Conversely, as miR-27b and miR-145 expression increased, the life expectancy of patients diagnosed with OSA and mCRC improved markedly. Conclusions: This study highlights the relevance of specific miRNAs on OSA in mCRCs and their significance as non-invasive biomarkers in predicting the prognosis in patients with mCRC and OSA.

The decentralized nature of traditional inter-domain routing protocols may lead to several issues, including convergence issues and proneness to misconfiguration. In response to these problems, alternative approaches that leverage the Software Defined Networking (SDN) paradigm to increase the control over routing operations have been recently proposed. In this context, Autonomous Systems (ASs) form a multi-domain network where routing tasks are delegated to an SDN controller. To perform inter-domain routing, each controller must learn how to reach any other node outside its domain. Thus, severe privacy concerns emerge, as the controllers need to access sensitive, business-critical information (e.g., links costs) of all the domains. Recently, protocols for computing the shortest path between a source and a destination (i.e., a common policy in routing tasks) in a privacy-preserving manner have been proposed. These protocols are based on Multi-Party Computation (MPC) schemes, which guarantee privacy at the cost of high computational and communication complexity, thus limiting scalability. In this paper, we exploit machine learning (ML) techniques to prune the network graph by removing the nodes with a low likelihood of being traversed by the shortest path. Privacy-preserving shortest path algorithms are then executed on the pruned graph, at a much lower complexity. Extensive experiments performed in multiple scenarios (varying topologies and number of nodes) indicate a major reduction of computational complexity (up to 75%) and communication complexity (up to 85%), at the expense of an acceptable increase in the average path cost (at most by 16%).

CISPR 11 and CISPR 32 define the radiated emission tests to be conducted in a semi-anechoic chamber equipped with controllable turntable and antenna mast, leading to an expensive and time-consuming test procedure. By noting the fact that table-top test setup usually involves long interconnecting cable bundle that radiates significantly, the work proposes a fast and simple pre-compliance radiated emission evaluation method based on cascaded Hertzian dipoles and its radiation theory. Several factors in the CISPR 11/32 test setups are integrated into this evaluation method to mimic a real test procedure. The accuracy of the proposed method is validated by an experimental test. A systematic analysis of the accuracy and applicability of the proposed method is also provided, showing that the method presents a simple, reliable and easy-to-be-implemented prediction tool for early-stage pre-compliance radiation evaluation, according to CISPR 11/32 testing.

Abstract Despite their widespread adoption, particle-scale simulation methods, such as the Discrete Element Method (DEM), for electrically charged particles in several natural processes and industrial transformations do not include realistic polarization effects. At close distances, these can dominate the particle motion and are impossible to predict by the commonly adopted Coulomb point-charge approximation. Sophisticated mathematical tools can account for uneven charge distributions, predicting an attractive force between a charged particle and a neutral particle or possible attraction between two like-charged particles. Such approaches are accurate but too complex for implementation in DEM simulations of many interacting particles. We propose a novel, simpler yet realistically accurate effective dipole model. By attributing a net charge and an induced effective dipole to each sphere, the interaction force between charged polarizable particles is computed in closed form. A comparison of a rigorous solution and the proposed dipole approach for two spherical particles reveals significant improvement over the commonly employed Coulomb law. The effects of particle size ratio and charge ratio on the interaction force are discussed. Then, the dynamic DEM simulation of a shaker filled with a binary mixture of differently sized particles that are all positively charged is shown to predict the counterintuitive formation of fine-on-coarse aggregates.

Abstract Breast cancer is the most commonly diagnosed type of cancer and the leading cause of cancer-related death in women worldwide. Highly targeted therapies have been developed for different subtypes of breast cancer, including hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-positive breast cancer. However, triple-negative breast cancer (TNBC) and metastatic breast cancer disease are primarily treated with chemotherapy, which improves disease-free and overall survival, but does not offer a curative solution for these aggressive forms of breast cancer. Moreover, the development of chemoresistance is a major cause of therapeutic failure in this neoplasia, leading to disease relapse and patient death. In addition, chemotherapy’s adverse side effects may substantially worsen health-related quality of life. Therefore, to improve the outcome of patients with breast cancer who are undergoing chemotherapy, several therapeutic options are under investigation, including the combination of chemotherapeutic drugs with natural compounds. Omega-3 (ω-3) polyunsaturated fatty acids (PUFAs), including docosahexaenoic and eicosapentaenoic acids, have drawn attention for their antitumoral properties and their preventive activities against chemotherapy-induced toxicities in breast cancer. A literature review was conducted on PubMed using keywords related to breast cancer, omega-3, chemoresistance, and chemotherapy. This review aims to provide an overview of the molecular mechanisms driving breast cancer chemoresistance, focusing on the role of ω-3 PUFAs in these recognized cellular paths and presenting current findings on the effects of ω-3 PUFAs combined with chemotherapeutic drugs in breast cancer management.

Abstract The greening of previously barren landscapes in the Arctic is one of the most relevant responses of terrestrial ecosystem to climate change. Analyses of satellite data (available since ~1980) have revealed a widespread tundra advance consistent with recent global warming, but the length is insufficient to resolve the long-term variability and the precise timing of the greening onset. Here, we measured plant-derived biomarkers from an Arctic fjord sediment core as proxies for reconstructing past changes in tundra vegetation during the transition from the Little Ice Age to modern warming. Our findings revealed a rapid expansion of the tundra since the beginning of the twentieth century, largely coinciding with the decline of summer sea ice extent and glacier retreat. The greening trend inferred from biomarker analysis peaked significantly in the late 1990s, along with a shift in the tundra community towards a more mature successional stage. Most of these signals were consistent with the biomolecular fingerprints of vascular plant species that are more adapted to warmer conditions and have widely expanded in proglacial areas during recent decades. Our results suggest that the greening of Arctic fjords may have occurred earlier than previously thought, improving our mechanistic understanding of vegetation-climate-cryosphere interactions that will shape tundra vegetation under future warming projections.

ABSTRACT: The objective of this randomized controlled experiment was to evaluate the effect of delaying induction of ovulation and timed artificial insemination (TAI) on expression of estrus before AI and first-service reproductive outcomes. A secondary objective was to evaluate the effects of delaying induction of ovulation in a Double-Ovsynch protocol on ovarian function. Lactating Holstein cows (n = 4,672) from 2 commercial dairy farms fitted with sensors for automated detection of estrus were synchronized with a Double-Ovsynch protocol up to the first PGF2α (PGF-L) of the Breeding-Ovsynch portion of the protocol (Pre-Ovsynch: GnRH, 7 d later PGF2α, 3 d later GnRH, 7 d later Breeding-Ovsynch: GnRH, 7 d later PGF2α, 1 d later PGF2α). At PGF-L, cows blocked by parity (primiparous vs. multiparous) and semen used for first service (sex-sorted dairy vs. conventional beef) were randomly assigned to the G56 (n = 2,338) or G80 (n = 2,334) treatments. Cows in G56 had 56 h whereas cows in G80 had 80 h from PGF-L to induction of ovulation with the last GnRH (GnRH2) before AI. For both treatments, TAI occurred ∼16 h after GnRH2. All cows with automated estrus alerts between PGF-L and TAI were inseminated at detected estrus (AIE) without GnRH. Ovarian function and responses to synchronization were monitored based on circulating concentrations of progesterone and examination of the ovaries by ultrasonography. Data for binary outcomes were analyzed by logistic and continuous outcomes with lineal regression. More cows in G80 received AIE and had estrus before AI. Overall, pregnancies per AI (P/AI) did not differ for the G80 and G56 treatments. Cows in G80 that received TAI and had no estrus had fewer P/AI than cows with estrus that received AIE or TAI in G80, and fewer P/AI than cows AIE and cows that received TAI and had or did not have estrus in the G56 treatment. No differences were observed between treatments or for cows with and without estrus for pregnancy loss. Unlike some minor differences between treatments for concentrations of progesterone at GnRH2, the most notable differences in ovarian function were for cows in both treatments with or without estrus that received TAI. Cows with estrus, were more likely to have follicles >16 mm, had larger follicles before ovulation, and had a greater ovulation risk after AI. Likewise, within the G80 treatment only, cows with estrus that received AIE or TAI had larger follicles, were more likely to have complete luteal regression, had greater ovulation risk, were more likely to have a functional corpus luteum, and had more circulating progesterone after AI. We concluded that delaying induction of ovulation and TAI was effective for allowing more cows to express estrus before AI, which had different ovarian function outcomes and greater P/AI than cows that did not express estrus. However, the greater P/AI of cows that expressed estrus was insufficient to compensate for the reduced P/AI of cows that did not express estrus, and thus increase overall P/AI compared with the treatment without delayed induction of ovulation. Detection of estrus before AI in cows undergoing synchronization of ovulation could help identify cows with different likelihoods of pregnancy after insemination.

Abstract Sorting grids to exclude the juveniles of species targeted by bottom trawl fisheries from the catch are among the most promising solutions to reduce discards. We tested a two-sections Juveniles’ Sorting Grid (JSG) in a Mediterranean fisheries restricted area. First, we provided information on the vitality of individuals escaping from the JSG bars during towing, by analysing underwater footage. Then, we evaluated the catch performance of the JSG-equipped trawl compared to a standard trawl by analysing both the full species community in the catches and the main commercial species. The probability for individuals to be alive while escaping from JSG was always higher than 65% (on average), with some species (e.g. red mullet, gurnards, 91–99% on average) showing significantly higher probability than others (e.g. European hake, crustaceans, 65–82% on average). The installation of a JSG in the trawl net did not change the overall catch composition in the codend, although significant differences were observed at the single species level. The JSG was effective at reducing undersized individuals of European hake, although a loss of legal-sized individuals was observed due to escapement. A significantly lower retention of the JSG-equipped trawl was also observed for other commercial species, such as deep-water rose shrimp and broadtail shortfin squid.

Abstract The present study aimed to investigate the causal relationships among cognitive impairment, psychopathology, and real-life functioning in a large sample of people with schizophrenia, using a data-driven causal discovery procedure based on partial ancestral graphs (PAGs). This method may provide additional insights for the identification of potential therapeutic targets to promote recovery in people with chronic schizophrenia. State-of-the-art instruments were used to assess the study variables. Two PAGs were generated at baseline and after 4 years of follow-up to model the nature of the causal relationships linking psychopathology, cognition, and functioning. The study sample was composed of more than 600 clinically stable patients with schizophrenia at two time points. The PAGs model indicated that working memory impairment is the first ancestor of the causal links, influencing all the other neurocognitive domains, social cognition, and functional capacity, which in turn affects everyday life functioning. From this domain of functioning a causal link is directed to disorganization and positive symptoms, and another to work skills and interpersonal relationships domains; the latter had a direct link to asociality and the other domains of negative symptoms. The structure of the PAGs did not differ significantly between baseline and follow-up, indicating the stability of the causal relationship model investigated cross-sectionally at both time points. The role of working memory impairment in the pathways to functional outcomes in schizophrenia highlights the importance of implementing integrated pharmacological and cognitive remediation interventions targeting neurocognition. The impact of everyday life and interpersonal functioning on the clinical presentation of schizophrenia suggests that integrated and personalized treatments, promoting relevant skills to improve these functional outcomes, may have a beneficial impact on clinical outcomes.

Abstract Ribosomes are responsible for the synthesis of proteins, the major component of cellular biomass. Classical experiments have established a linear relationship between the fraction of resources invested in ribosomal proteins and the rate of balanced growth of a microbial population. Very little is known, however, about how the investment in ribosomes varies over individual cells in a population. We therefore extended the study of ribosomal resource allocation from populations to single cells, using a combination of time-lapse fluorescence microscopy and statistical inference. We found a large variability of ribosome concentrations and growth rates in conditions of balanced growth of the model bacterium Escherichia coli in a given medium, which cannot be accounted for by the population-level growth law. A large variability in the allocation of resources to ribosomes was also found during the transition of the bacteria from a poor to a rich growth medium. While some cells immediately adapt their ribosome synthesis rate to the new environment, others do so only gradually. Our results thus reveal a range of strategies for investing resources in the molecular machines at the heart of cellular self-replication. This raises the fundamental question whether the observed variability is an intrinsic consequence of the stochastic nature of the underlying biochemical processes or whether it improves the fitness of Escherichia coli in its natural environment.

Abstract Addressing and mitigating decoherence sources plays an essential role in the development of a scalable quantum computing system, which requires low gate errors to be consistently maintained throughout the circuit execution. While nuclear spin-free materials, such as isotopically purified silicon, exhibit intrinsically promising coherence properties for electron spin qubits, the omnipresent charge noise, when converted to magnetic noise under a strong magnetic field gradient, often hinders stable qubit operation within a time frame comparable to the data acquisition time. Here, we demonstrate both open- and closed-loop suppression techniques for the transduced noise in silicon spin qubits, resulting in a more than two-fold (ten-fold) improvement of the inhomogeneous coherence time (Rabi oscillation quality) that leads to a single-qubit gate fidelity of over 99.6% even in the presence of a strong decoherence field gradient. Utilizing gate set tomography, we show that adaptive qubit control also reduces the non-Markovian noise in the system, which validates the stability of the gate fidelity. The technique can be used to learn multiple Hamiltonian parameters and is useful for the intermittent calibration of the circuit parameters with affordable experimental overhead, providing a useful subroutine during the repeated execution of general quantum circuits.

Abstract Studying how we explore the world in search of novelties is key to understand the mechanisms that can lead to new discoveries. Previous studies analyzed novelties in various exploration processes, defining them as the first appearance of an element. However, novelties can also be generated by combining what is already known. We hence define higher-order novelties as the first time two or more elements appear together, and we introduce higher-order Heaps’ exponents as a way to characterize their pace of discovery. Through extensive analysis of real-world data, we find that processes with the same pace of discovery, as measured by the standard Heaps’ exponent, can instead differ at higher orders. We then propose to model an exploration process as a random walk on a network in which the possible connections between elements evolve in time. The model reproduces the empirical properties of higher-order novelties, revealing how the network we explore changes over time along with the exploration process.

Fabrizio Martora,* Teresa Battista,* Antonella Giordano, Luca Potestio, Matteo Megna Dermatology Unit, Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy*These authors contributed equally to this workCorrespondence: Fabrizio Martora, Section of Dermatology - Department of Clinical Medicine and Surgery, University of Naples Federico II, Via Pansini 5, Napoli, 80131, Italy, Tel +39 - 081 – 7462457, Fax +39 - 081 – 7462442, Email fabriziomartora92@libero.itAbstract: Hypergammaglobulinemia is a sign of B cell and plasma cell hyperactivity marked by elevated levels of gamma globulins, proteins within the gamma fraction of serum electrophoresis, linked to diseases like acute hepatitis, Hodgkin’s lymphoma, autoimmune conditions, and neoplasms. Monoclonal gammopathy of undetermined significance (MGUS) is found in 3.2% of individuals over 50 and 5.3% over 70 due to immunosenescence, the gradual immune decline influenced by chronic infections, malnutrition, hormonal dysregulation, and smoking. This retrospective, single-center observational study explored the association between hypergammaglobulinemia and Hidradenitis Suppurativa (HS) based on sex, age, disease severity (IHS4 score), and Adalimumab treatment. Sixty patients (54% women, 46% men, average age 47) were observed over 12 months. Hypergammaglobulinemia was found in 68% of patients, with the highest prevalence in the 15– 29 age group (80%). It was also associated with increased disease severity, particularly in younger patients, who showed a reduced clinical response to Adalimumab (average HiSCR difference of 25%). While common inflammation markers like CRP and ESR remain essential for HS management, this study highlighted that hypergammaglobulinemia is more prevalent in younger patients with severe forms of HS. Unlike older patients, where immunosenescence can lead to more normal gamma globulin levels, younger patients demonstrated a strong link between chronic inflammation and disease. The findings suggest further investigation is needed to determine whether hypergammaglobulinemia is merely a marker or contributes to HS pathogenesis. If validated, hypergammaglobulinemia could be used to monitor disease progression and customize treatments. In conclusion, integrating immunological assessments into HS management could improve patient outcomes, particularly in younger demographics. With larger studies, hypergammaglobulinemia might be considered a predictive factor for HS, especially for severe or treatment-resistant cases.Keywords: hidradenitis suppurativa, hypergammaglobulinemia, immunosenescence

Abstract This randomized-controlled study evaluates the effectiveness of a newly developed social cognition rehabilitation intervention, the modified Social Cognition Individualized Activity Lab (mSoCIAL), in improving social cognition and clinical and functional outcomes of persons with schizophrenia recruited in two Italian sites: University of Campania “Luigi Vanvitelli” in Naples and ASST Fatebenefratelli-Sacco in Milan. mSoCIAL consists of a social cognitive training module focusing on different domains of social cognition and of a narrative enhancement module. We assessed changes in social cognition, clinical characteristics and functional variables in patients with schizophrenia who participated in 10 weekly sessions of mSoCIAL or received treatment as usual (TAU). A paired-sample t test and a repeated-measures MANOVA were used to investigate respectively within and between-group differences. Twenty people with schizophrenia were blindly assigned to mSoCIAL and 20 to TAU. After 10 weeks, mSoCIAL significantly improved disorganization, emotion recognition, functional capacity and real-life functioning. As compared to TAU, the mSoCIAL group showed a significant improvement in minimal and enriched social inference domain of theory of mind, and in key domains of real-life functioning (interpersonal relationships, everyday life skills, and work skills). mSoCIAL improved social cognition and real-life functioning of people with schizophrenia. These results highlight the importance of social cognition deficit treatment in schizophrenia and the necessity for these interventions to be multifaced and personalized. Such an approach ensures that improvements in social cognition translate into enhanced functional outcomes. Trial registration NCT05130853, registered on 24 November 2021.

Objetivo. Investigar cómo los temas relacionados con la mediación de la información en los museos se reflejan en la literatura científica de la Ciencia de la Información. Método. Investigación cualitativa y exploratoria utilizando la revisión integrativa de literatura como método de investigación bibliográfica. Se analizaron 14 artículos seleccionados en las bases de datos del Portal Brasileiro de Publicações Científicas de Acesso Aberto (Oasisbr), Repositórios Científicos de Acesso Aberto de Portugal (RCAAP), Red de Revistas Científicas de América Latina y el Caribe, España y Portugal (Redalyc), Scientific Electronic Library Online (SciELO), Red Latinoamericana para la Ciencia Abierta (LA Referencia) y Directory of Open Access Journals (DOAJ). Resultados. Se identificó la relación de pertinencia entre los conceptos de mediación cultural y mediación de la información. Conclusiones. Las aproximaciones teóricas sobre la mediación de la información en los museos muestran una conexión con los enfoques desarrollados desde el protagonismo social y en acciones dialécticas e interaccionis = Objective. To investigate how the issues related to the mediation of information in museums are reflected in the scientific literature in Information Science. Method. Qualitative, exploratory research, employing an integrative literature review to guide and systematize the bibliographic investigation. Fourteen articles were analyzed, selected from the following databases: Portal Brasileiro de Publicações Científicas em Acesso Aberto (Oasisbr), Repositórios Científicos de Acesso Aberto de Portugal (RCAAP), Red de Revistas Científicas de América Latina y el Caribe, España y Portugal (Redalyc), Scientific Electronic Library Online (SciELO), Red Latinoamericana para la Ciencia Abierta (LA Referencia) and Directory of Open Access Journals (DOAJ). Results. A significant relationship between the concepts of cultural mediation and information mediation was identified. Conclusions. Theoretical approaches to information mediation in museums, based on the reviewed literature are aligned with approaches that emphasize social protagonism, as well as dialectical and interactionist actions.

ABSTRACT: A primary objective of this randomized trial was to compare the percentage of cows that underwent clinical examination and were diagnosed with clinical health disorders (CHD) using a health monitoring program that relied only on automated monitoring system alerts versus a program that relied only on visual observation of clinical signs of disease to select cows for clinical examination. Another objective was to compare the effects of these health monitoring programs on milk yield, the herd exit dynamics (i.e., cows sold and dead), and first service reproductive outcomes. Lactating Holstein cows (n = 1,204) enrolled in the experiment were fitted with a neck-attached sensor of an automated monitoring system (HR Tags; Merck & Co. Inc.) that generated health alerts based on rumination time and activity. Milk yield was monitored 3 times per day by automated milk meters (MM27BC, DeLaval). Cows were blocked by parity, close-up period diet, and stratified by previous lactation milk yield, and then were randomly assigned within block to different programs for monitoring health from 3 to 21 DIM. Cows in the visual observation group (VO; n = 597) were selected for clinical examination exclusively based on visual observation of clinical signs of disease, whereas cows in the automated health monitoring group (AHM; n = 607) were selected for clinical examination based on health alerts consisting of the following: a health index score 20% in daily milk yield. Once selected for examination, the clinical exam was the same for both treatment groups. Binary data such as the occurrence of CHD, herd exit, and pregnancies per AI were analyzed with logistic regression. Daily and weekly milk yield were analyzed using ANOVA with repeated measurements. More cows underwent a clinical examination, more cows were diagnosed with at least one CHD, and more cows received treatment in the AHM group than the VO treatment group. Cows in the AHM treatment had more accumulated milk than cows in the VO treatment from 2 to 21 DIM. Cows in the AHM treatment diagnosed with at least 1 CHD produced more milk from 3 to 18 and 20 to 21 DIM than cows diagnosed with a CHD in the VO treatment. Fewer cows left the herd up to 21 DIM for the AHM than the VO treatment. Pregnancies per AI at first service were greater for the VO than the AHM treatment at 30 d but not at 50 d after AI, and no difference in pregnancy loss was detected. Overall, a health monitoring strategy that used automated health alerts increased the risk of undergoing clinical examination and having CHD diagnosed compared with a program that selected cows for clinical examination based exclusively on VO. Cows monitored with the program that relied on automated alerts also had greater milk yield in the first 21 DIM. Thus, monitoring cow health based on automated behavior and milk yield alerts might be a more effective alternative for health monitoring than exclusive use of visual observation of clinical signs of disease.

In recent years, the role of bioinformatics and computational biology together with omics techniques and transcriptomics has gained tremendous importance in biomedicine and healthcare, particularly for the identification of biomarkers for precision medicine and drug discovery. Differential gene expression (DGE) analysis is one of the most used techniques for RNA-sequencing (RNA-seq) data analysis. This tool, which is typically used in various RNA-seq data processing applications, allows the identification of differentially expressed genes across two or more sample sets. Functional enrichment analyses can then be performed to annotate and contextualize the resulting gene lists. These studies provide valuable information about disease-causing biological processes and can help in identifying molecular targets for novel therapies. This review focuses on differential gene expression (DGE) analysis pipelines and bioinformatic techniques commonly used to identify specific biomarkers and discuss the advantages and disadvantages of these techniques.

In medical practice, the retrieval of intravascular foreign bodies (IFBs) represents a challenge and often requires a multidisciplinary approach. We report a case of a 65-year-old male patient with a metallic guide wire extended from the right subclavian artery to the left ventricle. An interventional radiology team employed the “trap technique”, with a combination of a retrieval device and angiographic catheters, which results crucial in this case. Proper device management and imaging assessment are essentil to the successful retrieval of IFBs. Further research is warranted to refine IFB retrieval techniques and evaluate long-term outcomes.

Abstract Background Endocrine therapy (ET) has improved the clinical outcomes of Estrogen receptor alpha-positive (ERɑ +) breast cancer (BC) patients, even though resistance to ET remains a clinical issue. Mutations in the hormone-binding domain of ERɑ represent an acquired intrinsic mechanism of ET resistance. However, the latter also depends on the multiple functional interactions between BC cells and the tumor microenvironment (TME). Here, we investigated how the most common Y537S-ERɑ mutation may influence the behavior of fibroblasts, the most prominent component of the TME. Methods We conducted coculture experiments with normal human foreskin fibroblasts BJ1-hTERT (NFs), cancer-associated fibroblasts (CAFs), isolated from human BC specimens, and Y537S CRISPR-expressing MCF-7 BC cells (MCF-7YS). Mass spectrometry (MS) and Metacore analyses were performed to investigate how the functional interactions between BC cells/fibroblasts may affect their proteomic profile. The impact of fibroblasts on BC tumor growth and metastatic potential was evaluated in nude mice. Results Mutant BC conditioned medium (CM) affected the morphology/proliferation/migration of both NFs and CAFs. 198 deregulated proteins signed the proteomic similarity profile of NFs exposed to the YS-CM and CAFs. Among the upregulated proteins, Yes-associated protein 1 (YAP1) was the main central hub in the direct interaction network. Increased YAP1 protein expression and activity were confirmed in NFs treated with MCF-7YS-CM. However, YAP1 activation appears to crosstalk with the insulin growth factor-1 receptor (IGF-1R). Higher amount of IGF-1 were noticed in the MCF-7YS-CM cells compared to the MCF-7P, and IGF-1 immunodepletion reversed the enhanced YAP1 expression and activity. Mutant cells upon exposure to the NF- and CAF-CM exhibited an enhanced proliferation/growth/migration/invasion compared to the MCF-7P. MCF-7YS cells when implanted with CAFs showed an early relative increased tumor volume compared to YS alone. No changes were observed when MCF-7P cells were co-implanted with CAFs. Compared with that in MCF-7P cells, the metastatic burden of MCF-7YS cells was intrinsically greater, and this effect was augmented upon treatment with NF-CM and further increased with CAF-CM. Conclusions YS mutant BC cells induced the conversion of fibroblasts into CAFs, via YAP, which represent a potential therapeutic target which interrupt the functional interactions between mutant cells/TME and to be implemented in the novel therapeutic strategy of a subset of metastatic BC patients carrying the frequent Y537S mutations.

Objective: Explore the perceptions and attitudes of medical students regarding their education in opioid prescribing for pain management. Design: Three focus group discussions elicited open-ended, information-rich responses from medical students attending multiple institutions. Thematic analysis identified common themes from focus group transcript data. Setting: Rollins School of Public Health at Emory University, Atlanta, Georgia, USA. Participants: Medical students (n = 12) from four medical schools in the United States. Results: Focus group participants indicated they experienced changes in their perceptions and attitudes about opioids during their time in medical school, gradually recognizing the importance of treating pain while avoiding overprescribing and opioid-related harms. Discussions revealed that the curriculum on opioid medications and their prescription in medical school is limited and varied, with most opportunities for learning arising during preclinical years. The quantity and quality of the opioid-related education experienced by participants during medical school impacted their perceived knowledge about opioids and, consequently, their confidence in treating pain. Participants noted that important gaps in their knowledge about opioid prescribing persist, which may influence their future prescribing habits. While participants understood they had insufficient knowledge about opioid prescribing, they anticipated there would be additional learning during their residency programs. Conclusions: There is room for improvement for medical school instruction on the safe and effective use of opioids for pain management in the United States. Medical students themselves have expressed a desire for enhanced opioid education. Strengthening opioid education has implications across various healthcare environments, particularly in settings with prevalent opioid prescribing.

Substituting soybean meal (SM) with other protein sources can be advantageous in reducing production costs without increasing nitrogen losses in the environment. Peanut cake (PC) might be a strategy in ruminant herds to result in a performance similar to that observed in animals fed SM. This study assessed the PC inclusion at rates of 0, 250, 500, 750, and 1000 g/kg on intake and digestibility, performance, nitrogen balance, microbial protein synthesis, and carcass traits of lambs. Forty-five entire, crossbreed Dorper × Santa Inês lambs (average age = five months and 24.49 ± 5.27 kg of BW) were distributed in a completely randomized design. Only the ether extract intake was not affected by the PC inclusion, and only the crude protein digestibility was affected by the diets. The total weight and average daily gains decreased, and the feed conversion increased. Hot carcass yield was influenced quadratically, the leg depth increased and the loin-eye area decreased. The total replacement of soybean meal with peanut cake in diets for lambs did not compromise nutrient digestibility, microbial protein synthesis, and carcass characteristics. Nevertheless, peanut cake as a protein source in the diet had adverse effects on nutrient intake and growth performance of feedlot lambs.

Splenic injuries are common in abdominal trauma, as the spleen is one of the most often harmed organs. The treatment of splenic injuries underwent major changes during the past decades, shifting from a surgical approach to nonoperative management. This change of the proceedings results from a constantly growing awareness of the spleen’s crucial hematological and immunological function and was possible owing to the advances in radiological techniques. In a setting of high-energy trauma in hemodynamically stable patients, computed tomography (CT) remains the gold standard. Where ultrasonography (US) is of major importance is in cases of unstable patients undergone high-energy trauma or in patients after low-energy trauma. Nevertheless, baseline US’s sensitivity is not sufficient to detect splenic traumatic injuries; hence, a new method was developed involving ultrasound contrast agents (UCAs), called contrast-enhanced ultrasound (CEUS). In a low-energy trauma setting, it facilitates the diagnosis of abdominal lesions with a sensitivity close to that of CT, without the disadvantages of the latter. In addition, CEUS can be used in the follow-up of abdominal traumatic injuries. The fact that CEUS preserves CT’s sensitivity while not carrying the risk of radiation-induced cancer makes it feasible for children and pregnant women. This review aims to discuss the technical aspects of CEUS, the limitations, and possibilities regarding this modality, present the appearance of both a healthy and injured spleen, and compare CEUS’s effectiveness to that of CT through an analysis of retrievable studies.

Abstract Background Hemophilia B is a rare bleeding disorder in males, characterized by a deficiency in coagulation factor IX (FIX). Replacement of FIX with a recombinant FIX (rFIX) fusion protein, to sustain therapeutic plasma levels, is recommended as both treatment and prophylaxis to prevent bleeding episodes, particularly intracranial hemorrhage (ICH). Case presentation This case report outlines the management of ICH in a 7-month-old infant with severe hemophilia B, following an accidental trauma-related event, resulting in a thin compound fracture of the left occiput. FIX levels were extremely low (˂1.0%) and large deletions of the coagulation F9 gene (including exons 1–6) were identified. Intensive treatment with a rFIX fusion protein conjugated to the immunoglobulin Fc fragment (rFIXFc) continued for 18 days before hospital discharge. A continuous regimen of weekly rFIXFc infusions was implemented. Thirty days after initiating rFIXFc therapy, neutralizing antibodies or FIX inhibitors (common in patients with large F9 gene deletions) were observed, causing a diffuse skin rash. Such allergic reactions typically indicate progression to potentially serious nephrotic syndrome. A unique immunotolerance regimen of oral oxatomide and intravenous hydrocortisone was started to proactively prevent allergic reactions in this patient during rFIXFc prophylaxis. Even though low titers of the inhibitor (0.6–1.0 Bethesda units) were observed occasionally during subsequent follow-up, there were no signs of further allergies or development of nephrotic syndrome. Conclusion This is an uncommon case in which rFIXFc was continued despite the appearance of an allergic reaction and the development of FIX inhibitors. Subsequent allergic reactions were prevented with a combination of oral oxatomide and intravenous hydrocortisone given prior to prophylactic rFIXFc. Further studies are recommended to determine the usefulness of this combination with rFIX therapy.

The variation of mortality rates according to sex, regarding mortality from all causes and from specific conditions related to diabtes mellitus (DM) is widely discussed.

The omphalocele is an abdominal wall defect at the base of the umbilical cord, with the worldwide prevalence of 2.6 per 10,000 births. Omphalocele contains herniated abdominal organs and is classified in small and giant based on the size of the defect. Omphalocele is associated with several syndromes or structural anomalies. We reported a case of giant omphalocele of 6 cm with right lung agenesis with tracheal and right bronchial hypoplasia. Laryngeal mask stabilized the newborn allowing endotracheal intubation. Due to serious malformations, the newborn died after few hours of life for cardio-respiratory arrest. Early and accurate prenatal diagnosis allows a better intervention strategies in delivery room, improving the chances of survival and reducing complications for infants with omphalocele.

Abstract Despite all the efforts acquired in four years of the COVID-19 pandemic, the path to a full understanding of the biological mechanisms involved in this disease remains complex. This is partly due to a combination of factors, including the inherent characteristics of the infection, socio-environmental elements, and the variations observed within both the viral and the human genomes. Thus, this study aimed to investigate the correlation between genetic host factors and the severity of COVID-19. We conducted whole exome sequencing (WES) of 124 patients, categorized into severe and non-severe groups. From the whole exome sequencing (WES) association analysis, four variants (rs1770731 in CRYBG1, rs7221209 in DNAH17, rs3826295 in DGKE, and rs7913626 in CFAP46) were identified as potentially linked to a protective effect against the clinical severity of COVID-19, which may explain the less severe impact of COVID-19 on the Northern Region. Our findings underscore the importance of carrying out more genomic studies in populations living in the Amazon, one of the most diverse from the point of view of the presence of rare and specific alleles. To our knowledge, this is the first WES study of admixed individuals from the Brazilian Amazon to investigate genomic variants associated with the clinical severity of COVID-19.

Abstract Tele-support in breastfeeding can be defined as any support provided by a service that connects health workers and/or lactation consultants with breastfeeding parents through video visits, although a telephone contact with the breastfeeding mother remains the first method of remote breastfeeding support. The tele-support in breastfeeding has increased significantly during the SARS-CoV2 pandemic worldwide and, given its effectiveness, may be maintained also after the pandemic. The Italian Society of Neonatology on the basis of: 1) two focus group studies on the tele-support in breastfeeding conducted in Italy with 11 Neonatal Intensive Care Unit nurses and 10 neonatologists, respectively, 2) a national survey on tele-support in breastfeeding addressing the Italian Neonatal Intensive Care Units, and 3) a review of the available experiences and literature, has provided a Position Statement, limitedly to the individual tele-support in breastfeeding. The Italian Society of Neonatology states that: 1) the tele-support in breastfeeding can be used when a consultation in person is not shortly available and may allow to select those situations that require an in-person visit; 2) the organization of a tele-support in breastfeeding session requires the use of a competent, dedicated healthcare staff (specifically trained and/or with adequate experience) and an appropriate methodology while preparing, running and concluding the support session. According to Italian Society of Neonatology the tele-support in breastfeeding may be an effective intervention to promote breastfeeding as a complementary method to the in-person assistance and should be possibly provided in an integrated manner by the Community Health Services and the Maternity Hospital.

Background: Sarcopenia, a syndrome characterized by age-related loss of muscle mass and function, lacks universally accepted diagnostic criteria, particularly for its role as a prognostic factor in elderly patients with non-small-cell lung cancer (NSCLC). This study aimed to evaluate the prognostic significance of sarcopenia, assessed by psoas muscle size on baseline CT scans, in patients over 70 years of age with metastatic NSCLC. Methods: We retrospectively analyzed 85 elderly patients undergoing palliative radiation therapy between August 2022 and July 2024. Using morphometric analysis of psoas size, we investigated its correlation with overall survival (OS) and progression-free survival (PFS). Results: Our results showed that decreased psoas size was significantly associated with shorter OS and PFS, with median OS of 10 months and PFS of 4 months in sarcopenic patients compared to longer survival times in non-sarcopenic patients. Median survival of non-sarcopenic vs. sarcopenic patients was 21 ± 7 months (muscle area > median) versus 5 ± 2.3 months (muscle area < median). Multivariate analysis confirmed that psoas size, along with ECOG performance status and treatment of primary NSCLC, was a significant predictor of survival. Discussion: These findings suggest that psoas muscle size is a valuable prognostic marker for elderly NSCLC patients, potentially guiding treatment decisions and patient management. Further research is needed to validate these results and refine prognostic models for this population.

ABSTRACT: Our objectives were to develop and evaluate an integrated system consisting of a lateral flow immunoassay (LFIA) and an electronic portable imaging device for determination of pregnancy status of cows based on plasma concentrations of pregnancy-specific protein B (PSPB). Experiment 1 was conducted to test the performance of the LFIA for PSPB (PSPB-LFIA), whereas experiment 2 was conducted to evaluate the performance of the integrated system, including both the LFIA and imaging device. The PSPB-LFIA strips were made of nitrocellulose membrane with polystreptavidin, anti-mouse antibody, europium anti-PSPB conjugates, and biotin PSPB. After adding buffer and plasma in a 96-well plate, strips were dipped to initiate flow and were read in a fluorescence microscope to estimate PSPB concentrations based on the test-to-control line signal (T/C ratio). The T/C ratio of standards was linearly associated with PSPB (R2 = 0.99 in both experiments) concentrations. To test the ability to identify pregnant cows of the PSPB-LFIA only or the integrated system, plasma samples were collected and transrectal ultrasonography (TUS) was conducted 29 to 35 d after AI in lactating Holstein cows (experiment 1: n = 83; experiment 2: n = 205). A cow was considered pregnant (Preg) if concentrations of PSPB in plasma obtained by ELISA were ≥2 ng/mL or if an embryo was visible by TUS. In experiment 1, the accuracy of the PSPB-LFIA compared with ELISA was 92.7% (91.2% sensitivity [Se]; 96.1% specificity [Sp]; 98.1% positive predictive value [PPV]; 83.3% negative predictive value [NPV]) and compared with TUS was 90.4% (100% Se; 78.9% Sp; 84.9% PPV; 100% NPV). The agreement between LFIA and ELISA (kappa = 0.84; 95% CI 0.71–0.96) or LFIA and TUS (kappa = 0.80; 95% CI 0.67–0.93) as methods to classify cows as Preg or nonpregnant (Non-Preg) was high. In experiment 2, the accuracy of the PSPB-LFIA compared with ELISA was 96.1% (93.8% Se; 100% Sp; 100% PPV; 90.5% NPV) and compared with TUS was 92.2% (99.0% Se; 84.7% Sp; 87.6% PPV; 98.8% NPV). The agreement between LFIA and ELISA (kappa = 0.92; 95% CI 0.86–0.97) or LFIA and TUS (kappa = 0.84; 95% CI 0.77–0.92) as methods to classify cows as Preg or Non-Preg was high. We conclude that a system integrating a fluorescence-based LFIA and an optical reader was effective for classifying cows as pregnant or not pregnant based on estimations of plasma concentrations of PSPB. This novel system serves as a platform for further development of on-farm pregnancy testing tools based on measurement of biomarkers of pregnancy in bodily fluids of cattle.

ABSTRACT: Our overarching objective was to characterize associations between genomic merit for fertility and the reproductive function of lactating dairy cows in a prospective cohort study. In this manuscript, we present results of the association between genomic merit for fertility and indicators of metabolic status and inflammation, uterine health, endocrine status, response to synchronization, and estrous behavior in dairy cows. Lactating Holstein cows entering their first (n = 82) or second (n = 37) lactation were enrolled at parturition and fitted with an ear-attached sensor for automated detection of estrus. Ear-notch tissue samples were collected from all cows and submitted for genotyping using a commercial genomic test. Based on genomic PTA values for daughter pregnancy rate (gDPR), cows were classified into a high (Hi-Fert; gDPR >0.6; n = 36), medium (Med-Fert; gDPR −1.3 to 0.6; n = 45), or low (Lo-Fert; gDPR

Abstract This paper presents a comprehensive bibliometric review of the scientific literature on women’s entrepreneurship in agriculture across developed and developing countries. The paper delineates the evolving landscape, challenges, and opportunities that shape women’s entrepreneurship experiences in agriculture in the contexts of developed and developing countries. Through a detailed bibliometric analysis of 728 papers from 1992 to 2022, employing performance analysis and science mapping, our methodology distinguishes itself by quantifying contributions and mapping the thematic evolution within this domain. Our study reveals the significant contributions of women entrepreneurs to agricultural innovation, sustainability, and rural development while facing systemic biases, limited access to resources, and societal stereotypes that hinder their entrepreneurial path. The paper underscores the disparity in women’s entrepreneurship between developed and developing regions, with developed countries showcasing lower participation rates in agricultural entrepreneurship but a higher presence in decision-making roles within agribusinesses. In contrast, developing countries display a higher engagement of women in entrepreneurship, driven by necessity and marked by significant contributions to food security and economic stability, though under challenging conditions. Notably, the paper highlights the underrepresentation of women’s agricultural endeavours in scholarly research, pointing to a gap in the documentation and understanding of their contributions. The study reveals emerging themes such as digital agriculture, climate resilience, sustainability, and innovation, pointing towards future research directions that could further empower women in agriculture. It calls for more inclusive research and policy-making to recognise and support women’s vital role in agriculture, advocating for a holistic approach to address women entrepreneurs’ challenges in different economic contexts. Through this analysis, the paper contributes to a deeper understanding of gender dynamics in agricultural entrepreneurship and suggests pathways for fostering more equitable and sustainable agricultural practices.

Abstract We present a study of Ξ c 0 → Ξ 0 π 0 $$ {\Xi}_c^0\to {\Xi}^0{\pi}^0 $$ , Ξ c 0 → Ξ 0 η $$ {\Xi}_c^0\to {\Xi}^0\eta $$ , and Ξ c 0 → Ξ 0 η ′ $$ {\Xi}_c^0\to {\Xi}^0{\eta}^{\prime } $$ decays using the Belle and Belle II data samples, which have integrated luminosities of 980 fb −1 and 426 fb −1, respectively. We measure the following relative branching fractions B Ξ c 0 → Ξ 0 π 0 / B Ξ c 0 → Ξ − π + = 0.48 ± 0.02 stat ± 0.03 syst , B Ξ c 0 → Ξ 0 η / B Ξ c 0 → Ξ − π + = 0.11 ± 0.01 stat ± 0.01 syst , B Ξ c 0 → Ξ 0 η ′ / B Ξ c 0 → Ξ − π + = 0.08 ± 0.02 stat ± 0.01 syst $$ {\displaystyle \begin{array}{c}\mathcal{B}\left({\Xi}_c^0\to {\Xi}^0{\pi}^0\right)/\mathcal{B}\left({\Xi}_c^0\to {\Xi}^{-}{\pi}^{+}\right)=0.48\pm 0.02\left(\textrm{stat}\right)\pm 0.03\left(\textrm{syst}\right),\\ {}\mathcal{B}\left({\Xi}_c^0\to {\Xi}^0\eta \right)/\mathcal{B}\left({\Xi}_c^0\to {\Xi}^{-}{\pi}^{+}\right)=0.11\pm 0.01\left(\textrm{stat}\right)\pm 0.01\left(\textrm{syst}\right),\\ {}\mathcal{B}\left({\Xi}_c^0\to {\Xi}^0{\eta}^{\prime}\right)/\mathcal{B}\left({\Xi}_c^0\to {\Xi}^{-}{\pi}^{+}\right)=0.08\pm 0.02\left(\textrm{stat}\right)\pm 0.01\left(\textrm{syst}\right)\end{array}} $$ for the first time, where the uncertainties are statistical (stat) and systematic (syst). By multiplying by the branching fraction of the normalization mode, B Ξ c 0 → Ξ − π + $$ \mathcal{B}\left({\Xi}_c^0\to {\Xi}^{-}{\pi}^{+}\right) $$ , we obtain the following absolute branching fraction results B Ξ c 0 → Ξ 0 π 0 = 6.9 ± 0.3 stat ± 0.5 syst ± 1.3 norm × 10 − 3 , B Ξ c 0 → Ξ 0 η = 1.6 ± 0.2 stat ± 0.2 syst ± 0.3 norm × 10 − 3 , B Ξ c 0 → Ξ 0 η ′ = 1.2 ± 0.3 stat ± 0.1 syst ± 0.2 norm × 10 − 3 , $$ {\displaystyle \begin{array}{c}\mathcal{B}\left({\Xi}_c^0\to {\Xi}^0{\pi}^0\right)=\left(6.9\pm 0.3\left(\textrm{stat}\right)\pm 0.5\left(\textrm{syst}\right)\pm 1.3\left(\operatorname{norm}\right)\right)\times {10}^{-3},\\ {}\mathcal{B}\left({\Xi}_c^0\to {\Xi}^0\eta \right)=\left(1.6\pm 0.2\left(\textrm{stat}\right)\pm 0.2\left(\textrm{syst}\right)\pm 0.3\left(\operatorname{norm}\right)\right)\times {10}^{-3},\\ {}\mathcal{B}\left({\varXi}_c^0\to {\Xi}^0{\eta}^{\prime}\right)=\left(1.2\pm 0.3\left(\textrm{stat}\right)\pm 0.1\left(\textrm{syst}\right)\pm 0.2\left(\operatorname{norm}\right)\right)\times {10}^{-3},\end{array}} $$ where the third uncertainties are from B Ξ c 0 → Ξ − π + $$ \mathcal{B}\left({\Xi}_c^0\to {\Xi}^{-}{\pi}^{+}\right) $$ . The asymmetry parameter for Ξ c 0 → Ξ 0 π 0 $$ {\Xi}_c^0\to {\Xi}^0{\pi}^0 $$ is measured to be α Ξ c 0 → Ξ 0 π 0 = − 0.90 ± 0.15 stat ± 0.23 syst $$ \alpha \left({\Xi}_c^0\to {\Xi}^0{\pi}^0\right)=-0.90\pm 0.15\left(\textrm{stat}\right)\pm 0.23\left(\textrm{syst}\right) $$ .

Abstract Natural scenes are highly dynamic, challenging the reliability of visual processing. Yet, humans and many animals perform accurate visual behaviors, whereas computer vision devices struggle with rapidly changing background luminance. How does animal vision achieve this? Here, we reveal the algorithms and mechanisms of rapid luminance gain control in Drosophila, resulting in stable visual processing. We identify specific transmedullary neurons as the site of luminance gain control, which pass this property to direction-selective cells. The circuitry further involves wide-field neurons, matching computational predictions that local spatial pooling drive optimal contrast processing in natural scenes when light conditions change rapidly. Experiments and theory argue that a spatially pooled luminance signal achieves luminance gain control via divisive normalization. This process relies on shunting inhibition using the glutamate-gated chloride channel GluClα. Our work describes how the fly robustly processes visual information in dynamically changing natural scenes, a common challenge of all visual systems.

Abstract We report measurements of the e + e − → B B ¯ $$ B\overline{B} $$ , B B ¯ ∗ $$ B{\overline{B}}^{\ast } $$ , and B ∗ B ¯ ∗ $$ {B}^{\ast }{\overline{B}}^{\ast } $$ cross sections at four energies, 10653, 10701, 10746 and 10805 MeV, using data collected by the Belle II experiment. We reconstruct one B meson in a large number of hadronic final states and use its momentum to identify the production process. In the first 2 – 5 MeV above B ∗ B ¯ ∗ $$ {B}^{\ast }{\overline{B}}^{\ast } $$ threshold, the e + e − → B ∗ B ¯ ∗ $$ {B}^{\ast }{\overline{B}}^{\ast } $$ cross section increases rapidly. This may indicate the presence of a pole close to the threshold.

Abstract Background Community health workers (CHWs) are vital yet often invisible contributors to care coordination, health equity, and public health (PH) in medically underserved areas. The Atlanta Regional Community Health Workforce Advancement (ARCHWAy) Program leverages cross-sector partners to increase the number of CHWs on integrated care teams in metro Atlanta in the United States. Methods The ARCHWAy Program provides an innovative educational curriculum guided by United States Department of Labor CHW competencies and cross-walked with the Georgia CHW Initiative competencies. The 12-week in-person/online curriculum includes 155 h of content on becoming a CHW, mental health first aid, social determinants of health, trauma informed care, population health, community outreach, engagement, and capacity building, resiliency, communication, care coordination, advocacy, emergency preparedness, health promotion/disease prevention, 20 h of simulation including motivational interviewing, point of care testing, first aid, and 80 h of experiential learning through field placements. Project team members represent racial, ethnic, linguistic, and gender diversity ensuring culturally congruent content. Results Since program inception, the public health workforce in the region has been expanded by over 200 CHWs to date (goal of 446 CHWs) with specialized training offered in both English and Spanish. Discussion Positioning well-trained CHWs as members of integrated care teams promotes health equity by advancing PH, strengthening the PH workforce, reducing health disparities, and helping underserved populations address social determinants that can undermine health. The ARCHWAy program, by increasing CHW employment readiness through developing field placements with cross-sector partners, aspires to set the standard for apprenticeships in CHW training programs.

Abstract Background Parental malnutrition, particularly a low-protein diet (LPD), causes oligonephropathy at birth and predisposes offspring to hypertension and chronic kidney disease later in life. The onset of adult kidney disease varies based on genetics and environmental factors, often with subclinical alterations in kidney function being overlooked. This study aimed to examine changes in kidney morphology before significant kidney function decline in the offspring of mice fed a low-protein diet. Methods Using a combination of histological analysis, kidney metabolic and hemodynamic panel assessments, and advanced statistical techniques such as Linear Discriminant Analysis (LDA) and Principal Component Analysis (PCA), we investigated the initial impact of a maternal low-protein diet (LPD) on kidney development and function. Our study utilized 12-week-old F1 mice from F0 parents fed either a low-protein diet (LPD) or a normal-protein diet (NPD) before the onset of hypertension. Results The offspring (F1 generation) of parents (F0 generation) fed an LPD show reduced body weight from birth to P20. The kidney weight was also reduced compared to F1 offspring from parents fed an NPD. At 12 weeks of age, body weight normalized, but kidney weight remained low. Offspring of parents fed an LPD displayed abnormal kidney morphology, including dilated tubules, oligonephropathy, and fluid-filled cysts which had worsened with age. A kidney metabolic panel analysis at 12 weeks revealed a slight but consistent increase in urine albumin, plasma creatinine, mean urea, and BUN concentrations. Although no significant changes in hemodynamic variables were observed, 2/12 mice, both males, showed alterations in systolic blood pressure, suggesting sex-specific effects when comparing F1 mice from F0 fed either diet. Overall, kidney metabolic changes were strongly correlated to parental LPD. Conclusion Our findings indicate that significant kidney damage must accumulate in the F1 generation from parents fed an LPD before any detectable changes in blood pressure occur. Our study suggests that small variations in kidney metabolic function may point to early kidney damage and should not be overlooked in the offspring of these malnourished mice and likely humans.

Abstract Hole-based spin qubits in strained planar germanium quantum wells have received considerable attention due to their favorable properties and remarkable experimental progress. The sizeable spin-orbit interaction in this structure allows for efficient qubit operations with electric fields. However, it also couples the qubit to electrical noise. In this work, we perform simulations of a heterostructure hosting these hole spin qubits. We solve the effective mass equations for a realistic heterostructure, provide a set of analytical basis wavefunctions, and compute the effective g-factor of the heavy-hole ground state. Our investigations reveal a strong impact of highly excited light-hole states located outside the quantum well on the g-factor. We find that sweet spots, points of operations that are least susceptible to charge noise, for out-of-plane magnetic fields are shifted to impractically large electric fields. However, for magnetic fields close to in-plane alignment, partial sweet spots at low electric fields are recovered. Furthermore, sweet spots with respect to multiple fluctuating charge traps can be found under certain circumstances for different magnetic field alignments. This work will be helpful in understanding and improving the coherence of germanium hole spin qubits.

(1) Background: The observational retrospective study aimed to investigate the prevalence of personality disorders (PDs) and their association with psychopathological symptoms in a group of patients with cocaine addiction. (2) Methods: Ninety-five medical records of the Pathological Addictions Service of the National Health Service of Lecce (Italy) were analyzed. PDs were diagnosed using the Structured Clinical Interview for DSM-IV Axis II Personality Disorders (SCID-II) and psychopathological symptoms were investigated through the Symptom Checklist 90-Revised (SCL-90-R). (3) Results: Ninety-two out of ninety-five patients met the criteria for at least one PD (96.8%), almost 35% had two Cluster B PDs, and over 25% had three Cluster B PDs. Nine out of ninety-five people met the criteria for all Cluster B PDs. Among the Cluster B PDs, it emerged that the most frequent diagnosis was that of narcissistic–borderline–antisocial (over 20% of the total sample). The analysis highlighted that mental suffering is prevalent in those with multiple comorbid Cluster B PDs. Specifically, depression and psychoticism exceed the clinical cut-off (T score > 63) in all patient groups. At the same time, anxiety and obsessions–compulsions are complained of only by those with more than two PDs as well as the level of general distress. Furthermore, anxiety, hostility, and paranoid ideation are significantly higher in the group of patients with more than three PDs. (4) Conclusions: Further studies should better investigate the relationship between the two aspects and describe the causal effects of PDs on psychopathological symptoms or, on the contrary, the effects of the substance on mental health and the worsening of personality alterations.

Abstract We report a determination of the CKM angle ϕ 3, also known as γ, from a combination of measurements using samples of up to 711 fb −1 from the Belle experiment and up to 362 fb −1 from the Belle II experiment. We combine results from analyses of B + → DK +, B + → Dπ +, and B + → D * K + decays, where D is an admixture of D 0 and D ¯ 0 $$ {\overline{D}}^0 $$ mesons, in a likelihood fit to obtain ϕ 3 = (75.2 ± 7.6) ° . We also briefly discuss the interpretation of this result.

Abstract Background Necrotizing enterocolitis (NEC) is the most devastating gastrointestinal (GI) emergency in preterm neonates. Untargeted metabolomics may allow the identification of biomarkers involved in NEC pathophysiology. Methods We conducted a prospective study including preterm infants born at

Abstract Background Annually, about 4000 US children undergo a tracheostomy procedure to provide a functional, safe airway. In the hospital, qualified staff monitor and address problems, but post-discharge this responsibility shifts entirely to caregivers. The stress and constant demands of caregiving for a child with a tracheostomy with or without ventilator negatively affect caregivers. The aims of the study are to relieve the burden and stress experienced by caregivers at home, improve safety and outcomes for children post-discharge, and identify facilitators and barriers to implementation of comprehensive pediatric discharge programs. Methods The Boosting REsources and cAregiver empowerment for Tracheostomy care at HomE (BREATHE Study) is a pragmatic two-arm, randomized trial with six sites across the US. Caregivers of a child with a tracheostomy are randomized to comparator (“Trach Me Home”) or intervention (“Trach Plus”). The Comparator arm is the current gold standard focusing on caregiver education, technical skill building, and case management. The Intervention arm contains all elements of the Comparator plus educational resources, social support and communication with the outpatient pediatrician. Caregivers will complete three surveys: baseline (pre-discharge), 4-week and 6-month post-discharge. Outpatient pediatricians will complete a survey to assess self-confidence in caring for a child with tracheostomy and satisfaction with discharge communication. Interviews with clinicians and staff will identify facilitators and barriers to implementation. The study will examine whether the Intervention arm leads to lower caregiver burden, lower readmission rates and higher pediatrician satisfaction than Comparator arm. Discussion The BREATHE Study will advance our understanding of how hospitals can support caregivers with a child with a tracheostomy as they resume life, work, and family activities after discharge. Trial registration Registered on clinicaltrials.gov (NCT06283953). February 28, 2024.

ABSTRACT: The objective was to compare differences in reproductive performance for dairy cows grouped based on the combination of data for predictors available during the prepartum period and before the end of the voluntary waiting period (VWP), automated estrus alerts (AEA) during the VWP, and the combination of both factors. In a cohort study, data for AEA and potential predictors of the percentage of cows that receive AI at detected estrus (AIE), pregnancies per AI (P/AI) for first service, and the percentage of cows pregnant by 150 DIM (P150) were collected from −21 to 49 DIM for lactating Holstein cows (n = 886). The association between each reproductive outcome with calving season (cool, warm), calving-related events (yes, no), genomic daughter pregnancy rate (gDPR; high, medium, low), days in the close-up pen (ideal, not ideal), health disorder events (yes, no), rumination time (high or low CV prepartum and high or low increase rate postpartum), and milk yield (MY) by 49 DIM (high, medium, low) were evaluated in univariable and multivariable logistic regression models. Individual predictors (health disorders, gDPR, and MY) associated with the 3 reproductive outcomes in all models were used to group cows based on risk factors (RF; yes, n = 535 or no, n = 351) for poor reproductive performance. Specifically, cows were included in the RF group if any of the following conditions were met: the cow was in the high MY group, had low gDPR, or had at least 1 health disorder recorded. Cows were grouped into estrus groups during the VWP based on records of AEA (estrus VWP [E-VWP], n = 476 or no estrus VWP [NE-VWP], n = 410). Finally, based on the combination of levels of AEA and RF, cows were grouped into an estrus and no RF (E-NoRF, n = 217), no estrus and RF (NE-RF, n = 276), no estrus and no RF (NE-NoRF, n = 134), and estrus and RF (E-RF, n = 259) groups. Cows received AIE up to 31 d after the end of the VWP, and if they did not receive AIE, they received timed AI after an Ovsynch plus progesterone protocol. Logistic and Cox proportional hazard regression compared differences in reproductive outcomes for different grouping strategies. The NoRF (AIE: 76.9%; P/AI: 53.1%; P150: 84.5%) and E-VWP (AIE: 86.8%; P/AI: 44.8%; P150: 82.3%) groups had more cows AIE and higher P/AI and P150 than the RF (AIE: 64.5%; P/AI: 34.9%; P150: 72.9%) and NE-VWP (AIE: 50.0%; P/AI: 38.9%; P150: 72.1%) groups, respectively. When both factors were combined, the largest and most consistent differences were between the E-NoRF (AIE: 91.3%; P/AI: 58.7%; P150: 88.5%) and NE-RF groups (AIE: 47.3%; P/AI: 35.8%; P150: 69.5%). Compared with the whole population of cows or cows grouped based on a single factor, the E-NoRF and NE-RF groups had the largest and most consistent differences with the whole cow cohort. The E-NoRF and NE-RF groups also had statistically significant differences of a large magnitude when compared with the remaining cow cohort after removal of the respective group. We conclude that combining data for AEA during the VWP with other predictors of reproductive performance could be used to identify groups of cows with larger differences in expected reproductive performance than if AEA and the predictors are used alone.

ABSTRACT: The objectives of this prospective cohort study were to characterize associations among genomic merit for fertility with ovarian and endocrine function and the estrous behavior of dairy cows during an entire nonhormonally manipulated estrous cycle. Lactating Holstein cows entering their first (n = 82) or second (n = 37) lactation had ear-notch tissue samples collected for genotyping using a commercial genomic test. Based on genomic predicted transmitting ability values for daughter pregnancy rate (gDPR), cows were classified into high (Hi-Fert; gDPR > 0.6, n = 36), medium (Med-Fert; gDPR −1.3 to 0.6, n = 45), and low fertility (Lo-Fert; gDPR < −1.3, n = 38) groups. At 33 to 39 DIM, cohorts of cows were enrolled in the Presynch-Ovsynch protocol for synchronization of ovulation and initiation of a new estrous cycle. Thereafter, the ovarian function and endocrine dynamics were monitored daily until the next ovulation by transrectal ultrasonography and concentrations of progesterone (P4), estradiol, and FSH. Estrous behavior was monitored with an ear-attached automated estrus detection system that recorded physical activity and rumination time. Overall, we observed an association between fertility group and the ovarian and hormonal phenotype of dairy cows during the estrous cycle. Cows in the Hi-Fert group had greater circulating concentrations of P4 than cows in the Lo-Fert group from d 4 to 13 after induction of ovulation and from day −3 to −1 before the onset of luteolysis. The frequency of atypical estrous cycles was 3-fold greater for cows in the Lo-Fert than the Hi-Fert group. We also observed other modest associations between genomic merit for fertility with the follicular dynamics and estrous behavior. We found several associations between milk yield and parity with ovarian, endocrine, and estrous behavior phenotypes as cows with greater milk yield and in the second lactation were more likely to have unfavorable phenotypes. These results demonstrate that differences in reproductive performance between cows of different genomic merit for fertility classified based on gDPR may be partially associated with circulating concentrations of P4, the incidence of atypical phenotypes during the estrous cycles, and, to a lesser extent, the follicular wave dynamics. The observed physiological and endocrine phenotypes might help explain part of the differences in reproductive performance between cows of superior and inferior genomic merit for fertility.

The main task of this work is the optimization of the manufacturing process of Al-alloy lattice cellular structures with rhombic cell, obtained with lost-PLA technique. It is an easy, environment sustainable and economical technique (both for infrastructure and operating costs) for the manufacturing of Al porous structure based on the 3D printing of PLA and replication process alternative to that based on expensive metal 3D printers. Plaster processing, PLA burnout and AA 6082 alloy casting conditions and parameters have been suitably tuned in order to get final samples with geometry and surface finishing conditions identical to the starting ones made in PLA. A good replication process has been implemented with a high repeatability rate and accurate surface finishing, comparable with that of the PLA printed objects. Morphological analysis on PLA and Al 6082 was conducted as well microstructural analysis and Vickers microhardness tests on Al alloy samples in the as-cast conditions. Metallography reveals the presence of AlFeSi and AlFeMnSi intermetallic phases at the cell boundaries and some coarse precipitates Mg2Si in the AA 6082 alloy. Microstructures and HV measured values are aligned with literature data for this alloy in the same (as-cast) conditions.

Abstract Assessing pain in newborns in the NICU is crucial due to their frequent exposure to painful stimuli, yet it's challenging due to the subjective nature of current methods. This study aimed to evaluate the effectiveness of an AI system designed for automatic facial recognition by comparing its performance with the expert opinion of health care provider. This is a secondary analysis from an eye-tracking study, assessing neonatal pain evaluations by healthcare professionals. The performance of AI software, FaceReader 9, was compared to experts' evaluations using a visual-analog scale, focusing on identifying specific facial action units associated with different pain levels. The study found significant differences in AI-generated metrics—arousal and valence—across three stimulus types: non-noxious thermal, short-noxious, and prolonged-noxious, with p-values below 0.001. A strong correlation (r = 0.84, p ≤ .001) was observed between AI metrics and expert ratings. Eleven facial action units were identified as relevant to describe neonatal pain. The findings highlight the AI system's potential in accurately detecting and analyzing newborn facial expressions in response to varying pain intensities, demonstrating a significant correlation with healthcare professionals' assessments. This suggests that AI technology could enhance objective pain assessment in neonates.

Abstract We present the result of a search for the charged-lepton-flavor violating decay τ − → μ − μ + μ − using a 424 fb −1 sample of data recorded by the Belle II experiment at the SuperKEKB e + e − collider. The selection of e + e − → τ + τ − events is based on an inclusive reconstruction of the non-signal tau decay, and on a boosted decision tree to suppress background. We observe one signal candidate, which is compatible with the expectation from background processes. We set a 90% confidence level upper limit of 1.9 × 10 −8 on the branching fraction of the τ − → μ − μ + μ − decay, which is the most stringent bound to date.

Abstract Bone sarcomas are malignant tumors of mesenchymal origin. Complete surgical resection is the cornerstone of multidisciplinary treatment. However, advanced, unresectable forms remain incurable. A crucial step towards addressing this challenge involves comprehending the molecular mechanisms underpinning tumor progression and metastasis, laying the groundwork for innovative precision medicine-based interventions. We previously showed that tyrosine kinase receptor Ephrin Type-A Receptor 2 (EphA2) is overexpressed in bone sarcomas. EphA2 is a key oncofetal protein implicated in metastasis, self-renewal, and chemoresistance. Molecular, genetic, biochemical, and pharmacological approaches have been developed to target EphA2 and its signaling pathway aiming to interfere with its tumor-promoting effects or as a carrier for drug delivery. This review synthesizes the main functions of EphA2 and their relevance in bone sarcomas, providing strategies devised to leverage this receptor for diagnostic and therapeutic purposes, with a focus on its applicability in the three most common bone sarcoma histotypes: osteosarcoma, chondrosarcoma, and Ewing sarcoma.