bluuebunny/crossref_metadata_2025 huggingface dataset:
Diagnostic accuracy of saliva-based testing as a Vibrio cholerae surveillance tool among naturally infected patients
Authors: Chisenga Caroline C , Phiri Bernard , Ng’ombe Harriet , Muchimba Mutinta , Liswaniso Fraser , Bernshtein Biana , Cunningham Adam F , Sack David , Bosomprah Samuel
Published: October 2024

Saliva, as a diagnostic medium, offers a promising alternative to blood by virtue of its non-invasive collection, which enhances patient compliance, especially in paediatric and geriatric populations. In this study, we assessed the utility of saliva as a non-invasive medium for measuring Vibrio cholerae-specific serum antibodies in naturally infected individuals. We tested paired serum and saliva samples obtained from a total of 63 patients with cholera enrolled in a cohort study. Vibriocidal antibodies assay (IgM/IgG) as markers for accurate determination was used to determine cholera-specific antibody levels. Using receiver operating characteristics (ROC) curve, we found that the best cut-off that maximizes (sensitivity + specificity) is 10 titres. At this saliva titre, the sensitivity is 76.9% (95%CI: 60.9%, 87.7%) and specificity is 80.0% (95%CI: 56.6%, 92.5%). Using Spearman’s correlation coefficient, we also found evidence of a positive correlation between V. cholerae saliva and serum antibodies (rho = 0.66, P < 0.001). In conclusion, saliva-based diagnostic cholera tests have high diagnostic accuracy and would be advantageous, cheaper, and quicker for early diagnosis of severe cholera outcomes.
Multi-scale spiking network model of human cerebral cortex
Authors: Pronold Jari , van Meegen Alexander , Shimoura Renan O , Vollenbröker Hannah , Senden Mario , Hilgetag Claus C , Bakker Rembrandt , van Albada Sacha J
Published: October 2024

Although the structure of cortical networks provides the necessary substrate for their neuronal activity, the structure alone does not suffice to understand the activity. Leveraging the increasing availability of human data, we developed a multi-scale, spiking network model of human cortex to investigate the relationship between structure and dynamics. In this model, each area in one hemisphere of the Desikan–Killiany parcellation is represented by a $1\,\mathrm{mm^{2}}$ column with a layered structure. The model aggregates data across multiple modalities, including electron microscopy, electrophysiology, morphological reconstructions, and diffusion tensor imaging, into a coherent framework. It predicts activity on all scales from the single-neuron spiking activity to the area-level functional connectivity. We compared the model activity with human electrophysiological data and human resting-state functional magnetic resonance imaging (fMRI) data. This comparison reveals that the model can reproduce aspects of both spiking statistics and fMRI correlations if the inter-areal connections are sufficiently strong. Furthermore, we study the propagation of a single-spike perturbation and macroscopic fluctuations through the network. The open-source model serves as an integrative platform for further refinements and future in silico studies of human cortical structure, dynamics, and function.
Machine Learning-Based Detection of Bladder Cancer by Urine cfDNA Fragmentation Hotspots that Capture Cancer-Associated Molecular Features
Authors: Meng Xiang-Yu , Zhou Xiong-Hui , Li Shuo , Shi Ming-Jun , Li Xuan-Hao , Yang Bo-Yu , Liu Min , Yi Ke-Zhen , Wang Yun-Ze , Zhang Hong-Yu , Song Jian , Wang Fu-Bing , Wang Xing-Huan
Published: October 2024

Background

cfDNA fragmentomics-based liquid biopsy is a potential option for noninvasive bladder cancer (BLCA) detection that remains an unmet clinical need.

Methods

We assessed the diagnostic performance of cfDNA hotspot-driven machine-learning models in a cohort of 55 BLCA patients, 51 subjects with benign conditions, and 11 healthy volunteers. We further performed functional bioinformatics analysis for biological understanding and interpretation of the tool’s diagnostic capability.

Results

Urinary cfDNA hotspots-based machine-learning model enabled effective BLCA detection, achieving high performance (area under curve 0.96) and an 87% sensitivity at 100% specificity. It outperformed models using other cfDNA-derived features. In stage-stratified analysis, the sensitivity at 100% specificity of the urine hotspots-based model was 71% and 92% for early (low-grade Ta and T1) and advanced (high-grade T1 and muscle-invasive) disease, respectively. Biologically, cfDNA hotspots effectively retrieved regulatory elements and were correlated with the cell of origin. Urine cfDNA hotspots specifically captured BLCA-related molecular features, including key functional pathways, chromosome loci associated with BLCA risk as identified in genome-wide association studies, or presenting frequent somatic alterations in BLCA tumors, and the transcription factor regulatory landscape.

Conclusions

Our findings support the applicability of urine cfDNA fragmentation hotspots for noninvasive BLCA diagnosis, as well as for future translational study regarding its molecular pathology and heterogeneity.
Is metadata of articles about COVID-19 enough for multilabel topic classification task?
Authors: Xu Shuo , Zhang Yuefu , Chen Liang , An Xin
Published: October 2024

The ever-increasing volume of COVID-19-related articles presents a significant challenge for the manual curation and multilabel topic classification of LitCovid. For this purpose, a novel multilabel topic classification framework is developed in this study, which considers both the correlation and imbalance of topic labels, while empowering the pretrained model. With the help of this framework, this study devotes to answering the following question: Do full texts, MeSH (Medical Subject Heading), and biological entities of articles about COVID-19 encode more discriminative information than metadata (title, abstract, keyword, and journal name)? From extensive experiments on our enriched version of the BC7-LitCovid corpus and Hallmarks of Cancer corpus, the following conclusions can be drawn. Our framework demonstrates superior performance and robustness. The metadata of scientific publications about COVID-19 carries valuable information for multilabel topic classification. Compared to biological entities, full texts and MeSH can further enhance the performance of our framework for multilabel topic classification, but the improved performance is very limited.

Database URL: https://github.com/pzczxs/Enriched-BC7-LitCovid
Measuring concern about smile appearance among adults
Authors: Silva Bianca Nubia Souza , Campos Lucas Arrais , Martins Bianca Gonzalez , Marôco João , Peltomäki Timo , Campos Juliana Alvares Duarte Bonini
Published: October 2024

Background/Objectives

To adapt and estimate the psychometric properties of Utrecht Questionnaire for esthetic outcome assessment in rhinoplasty (OAR) to assess concern about smile appearance and to estimate the influence of demographic characteristics on this concern in adults.

Material/Methods

This was a cross-sectional observational study. Individuals aged between 18 and 40 years participated in the study. The Portuguese version of OAR was adapted for smile assessment in dental practice and was named Questionnaire for Outcome Assessment of Smile Aesthetic (OA-Smile). Data validity was estimated using factorial validity [confirmatory factor analysis (CFA)—CFI, Tucker-Lewis index (TLI), SRMR)] and convergent validity (average variance extracted). Reliability was assessed using the alpha ordinal coefficient (αordinal) and the omega coefficient (ω). A structural model was elaborated to assess the contribution of demographic characteristics to smile appearance concerns. Model fit was evaluated, and the z-test (α = 5%) was used to estimate the significance of the path estimates (β).

Results

2.523 subjects participated in the study [mean age = 32.86 (SD = 11.39) years, 68.1% female]. The factor model of orofacial appearance (OA)-Smile presented an adequate fit to the data [CFA: comparative fit index (CFI) = 0.99, TLI = 0.99, SRMR ≤ 0.05]. Convergent validity (AVE ≥ 0.80) and reliability (αordinal and ω ≥ 0.85) were adequate. The structural model presented an acceptable fit (CFI = 0.974; TLI = 0.991 and SRMR = 0.053). Women, younger people, single people, people with lower income, people using dental prostheses, undergoing dental treatment, and those who do not like their smile were more concerned about their smile appearance.

Limitations

Nonprobability sampling, online data collection, and cross-sectional design are considered limitations of the study.

Conclusions/Implications

OA-Smile is a suitable scale to assess smile appearance concerns, and the data obtained with this scale were valid and reliable. Demographic characteristics should be considered when measuring concerns about smile appearance.
A caution on sibling comparisons in studying effects of the rearing environment
Authors: Engzell Per , Hällsten Martin
Published: October 2024

Recent studies use sibling fixed effects to estimate the influence of the family environment on children, a practice we call the ‘discordant family design’. These studies suffer from a disconnect between the use of within-family variation, on the one hand, and relevant theories which mostly refer to variation between families on the other. In addition, reverse causality, within-family confounding, selection into identification, and measurement error complicate their interpretation further. We discuss three applied examples—the effects of parenting, family income, and neighbourhood context—and provide some general guidance. To avoid misinterpretation, researchers should have a strong grasp of the variance that enters into estimation, and not just the potential confounders a given strategy is designed to deal with.
Major clinical outcomes in symptomatic vs. asymptomatic atrial fibrillation: a meta-analysis
Authors: Karakasis Paschalis , Pamporis Konstantinos , Siontis Konstantinos C , Theofilis Panagiotis , Samaras Athanasios , Patoulias Dimitrios , Stachteas Panagiotis , Karagiannidis Efstratios , Stavropoulos George , Tzikas Apostolos , Kassimis George , Giannakoulas George , Karamitsos Theodoros , Katritsis Demosthenes G , Fragakis Nikolaos
Published: October 2024

Background and Aims

Current guidelines suggest that asymptomatic atrial fibrillation (AF) is independently associated with increased risks of stroke and mortality compared with symptomatic AF. Considering that recent investigations have provided conflicting results, the present study aimed to evaluate the association between symptom status and clinical outcomes in patients with AF.

Methods

Medline, Cochrane Library, and Scopus were searched until 25 March 2024. Triple-independent study selection, data extraction and quality assessment were performed. Evidence was pooled using random-effects meta-analyses.

Results

Thirty-six studies (217 850 participants) were included. Based on the frequentist analysis, symptomatic individuals had no significant difference in the risk of all-cause mortality [hazard ratio (HR) .97, 95% confidence interval (CI) .80–1.17], cardiovascular mortality (HR 1.04, 95% CI .72–1.49), thromboembolism (HR 1.06, 95% CI .87–1.28), stroke (HR 1.06, 95% CI .84–1.34), hospitalization (HR 1.34, 95% CI .89–2.02), and myocardial infarction (HR .98, 95% CI .70–1.36), compared to the asymptomatic group. Symptomatic patients had a 33% increased risk of new-onset heart failure (HR 1.33, 95% CI 1.19–1.49) and a 30% lower risk of progression to permanent AF (HR .70, 95% CI .54–.89). The Bayesian analysis yielded comparable results, yet the association between symptom status and new-onset heart failure was not significant (HR 1.27, 95% credible interval .76–1.93; Bayes factor = 1.2). Symptomatic patients had higher odds of receiving antiarrhythmic drugs (odds ratio [OR] 1.64, 95% CI 1.33–2.03) and ablation therapy (OR 1.47, 95% CI 1.06–2.05) compared to asymptomatic cases.

Conclusions

The risk of major clinical outcomes did not differ between individuals with and without AF-related symptoms. Asymptomatic patients had a greater hazard of progression to permanent AF.
Factors associated with patient activation in people with heart failure based on the individual and family self-management theory: a cross-sectional study
Authors: Wei Shuangshuang , Zhou Yu , Shu Pan , Jiang Xiaolian
Published: October 2024

Aims

Patient activation (PA) is crucial for effective self-management of people with heart failure (HF). Clarifying factors associated with PA might be important to develop interventions to promote PA. This study aimed to explore context factors associated with PA in people with HF.

Methods and results

Two hundred and sixty-eight patients were enrolled in a cross-sectional study (median age = 65 years). We surveyed variables based on context factors of the individual and family self-management theory, including demographic and disease factors, quality of chronic care, family function, and depression. Correlation analysis was conducted for data analysis, and path analysis was used to verify our hypothesis model about context factors and PA. The median PA score was 51.10. Path analysis showed that age, educational level, living arrangement, device therapy, quality of chronic care, family function, and depression were directly or indirectly related to PA. The quality of chronic care mediated the associations between device therapy and educational level and PA. Age, educational level, living arrangement, and quality of chronic care affected family function and then affected activation. Depression mediated the relationships between the quality of chronic care, educational level, family function, and PA.

Conclusion

This study increased the understanding of factors associated with PA in the HF population. When assessing PA in people with HF, those who are older, have a low educational level, and living alone need more attention from healthcare professionals. Interventions focusing on improving the quality of chronic care, family function, and depression might help activate people to practice self-management.
Characterizing the evolution of defense in a tripartite marine symbiosis using adaptive dynamics
Authors: Singh Prerna , Bruijning Marjolein , Carver Gavriela D , Donia Mohamed S , Metcalf Charlotte Jessica E
Published: October 2024

The evolution and maintenance of symbiotic systems remains a fascinating puzzle. While the coevolutionary dynamics of bipartite (host–symbiont) systems are well-studied, the dynamics of more complex systems have only recently garnered attention with increasing technological advances. We model a tripartite system inspired by the marine symbiotic relationship between the alga Bryopsis sp., its intracellular defensive bacterial symbiont “Candidatus Endobryopsis kahalalidifaciens,” which produces a toxin that protects the alga against fish herbivores, and the sea-slug Elysia rufescens (Zan et al., 2019), which is not deterred by the toxin. We disentangle the role of selection on different actors within this system by investigating evolutionary scenarios where defense evolves as (i) a host-controlled trait that reduces algal reproductive ability; (ii) a symbiont-controlled trait that impacts symbiont transmission; and (iii) a trait jointly controlled by both host and symbiont. Optimal investment in defensive toxins varies based on the characteristics of the host, symbiont, and sea slug; and evolutionary trajectories are modulated by trade-off shape, i.e., a strongly decelerating trade-off between defense and symbiont transmission can drive symbiont diversification via evolutionary branching. Increasing slug herbivory reduces host investment in defense to favor reproduction, while symbiont investment in defense first declines and then increases as host density declines to the degree that horizontal symbiont transmission is no longer beneficial. Increasing vertical transmission selects for reduced defense by the host when it evolves as a jointly controlled trait, as a result of investment by the symbiont. Our theoretical exploration of the evolution of defensive symbiosis in scenarios involving interactions with multiple herbivores provides a first window into the origin and maintenance of the Bryopsis sp. system, and adds another piece to the puzzle of the evolution of symbiotic systems.
From the economic to the pandemic crisis: The impact upon the EU constitutional architecture—Introduction to the Symposium
Authors: Torres Pérez Aida , Solanes Mullor Joan
Published: October 2024

The European Union has evolved significantly, shaped by crises as foreseen by Jean Monnet, who predicted that Europe would be “forged in crises.” Over recent decades, it has faced challenges such as the euro crisis, the COVID-19 pandemic, Brexit, rule-of-law backsliding, and ongoing geopolitical conflicts. These crises have tested and transformed the European Union’s constitutional framework, prompting institutional reforms and innovations in governance without necessarily revising the Treaties. This Symposium explores the European Union’s constitutional evolution through the lens of crises. Key reforms include the reinforcement of budgetary discipline during the euro crisis and the shift toward a stimulus-based approach in response to the pandemic, culminating in the NextGenerationEU framework. Contributors analyze the model of economic governance that has evolved from the convergence of both the economic and pandemic crises, the changing role of regions, the judiciary’s evolving oversight functions and its limits, and rule of law conditionality as a distinctive form of governance. The Symposium will delve into the post-crisis governance landscape of the European Union from a constitutional perspective, focusing on the structural adjustments implemented and their enduring impact. Despite these changes, the European Union has demonstrated resilience and adaptability, forging new governance structures that reflect its deepening constitutional identity. In the end, the Symposium provides a comprehensive examination of these shifts, highlighting how the European Union continues to integrate and innovate in response to ongoing challenges.
Maternal Immunization
Authors: Cho Hye-Kyung , Frivold Collrane , Chu Helen Y
Published: October 2024

Pregnant individuals and infants are at risk from vaccine-preventable diseases like severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza. Maternal vaccination during pregnancy can protect both the mother and child. Recent progress in developing these vaccines is notable, but vaccine hesitancy and the exclusion of pregnant individuals from clinical trials limit their use. Maternal immunization safeguards mothers from severe illness and adverse pregnancy outcomes while providing infants with antibodies through the placenta and breast milk. Inactivated vaccines are generally effective and safe during pregnancy. Limited safety and efficacy data due to exclusion from trials hinder vaccine uptake; however, vaccines like tetanus-diphtheria-acellular pertussis (Tdap), influenza, and SARS-CoV-2 have proven effective, and are recommended vaccines during pregnancy. New vaccines for group B Streptococcus (GBS) and cytomegalovirus are in development, with the GBS vaccine being the most advanced. Combating vaccine hesitancy through strong health care provider recommendations is vital to enhance uptake and protect pregnant individuals and their infants.
Pathological Insights into Lassa Virus-Induced Vestibular Dysfunction in Mice: Histopathological Analysis of the Inner Ear Vestibular Apparatus
Authors: Suzuki Tomoharu , Saito Marina Hosotani , Lin Nantian , Tamura Atsushi , Yun Nadezhda , Koma Takaaki , Maruyama Junki , Paessler Slobodan , Makishima Tomoko
Published: October 2024

Lassa fever (LF), caused by Lassa virus (LASV) infection, typically leads to mild symptoms in humans, but some survivors experience audiovestibular problems. Here we present vestibular histopathological insights in our LF model mice. We observed (1) hemorrhage within the vestibular ganglion and stroma beneath the sensory epithelium, (2) preserved hair cells and supporting cells, (3) LASV antigen presence in the vestibular ganglion cells and the stroma beneath the sensory epithelium, and (4) CD3-positive T-lymphocyte infiltration in the vestibular ganglion and the stroma underlying the sensory epithelium. LASV and/or its immune response likely contributes to the pathogenesis of vestibular dysfunction.
Trace mineral sources influence in vitro fermentation characteristics and trace mineral solubility
Authors: Loh Huey Yi , Spears Jerry W , Guimaraes Octavio , Miller Alexandra C , Thomas Tyler A , Engle Terry E
Published: October 2024

Two experiments were conducted to determine: 1) the impact of strained rumen fluid (SRF) alone or SRF with particle-associated microorganisms (PAO) included and dilution on in vitro dry matter digestibility (DMD) and 2) the impact of trace mineral (TM) source on in vitro fermentation characteristics and TM solubility under simulated abomasal and intestinal conditions. In experiment 1, 3 cannulated steers were adapted to a diet formulated to meet the nutrient requirements for lactating dairy cows. Strained RF was obtained by straining rumen content through 2 layers of cheesecloth. Half of the remaining digesta was washed with McDougall’s buffer and filtered through 2 layers of cheesecloth to obtain PAO. Both SRF and PAO were filtered again through 8 layers of cheesecloth. Strained RF was mixed with either McDougall’s buffer (SRF) or PAO (SRF+ + PAO) at a ratio of 1:2 or 1:4 and incubated at 39 °C for 12 h using the ground basal diet as the substrate. Digestibility of DM was greater in digestion tubes containing SRF and SRF + PAO at a 1:2 ratio. In experiment 2, 8 steers fitted with a ruminal cannula were blocked by body weight and assigned to 1 of the 2 treatment groups. Treatments consisted of 10 mg Cu, 40 mg Mn, and 60 mg Zn/kg DM from either: 1) sulfate (STM) or 2) hydroxychloride (HTM) sources. Steers were housed in individual pens and fed the same diet as described in experiment 1. Dietary TM treatments were mixed with dried distiller grains and mixed in the diet, by hand, immediately after basal diet delivery. Dietary treatments were fed for 14 d. On day 15, SRF + PAO was collected from each steer (STM-RF and HTM-RF) and used in a series of in vitro crossover experiments. In vitro substrates (S) used were the ground diets consumed by the animals on each treatment (STM-S and HTM-S). Incubations containing HTM-S had greater (P < 0.01) total volatile fatty acid (VFA) concentration and propionic acid molar proportions, but lesser (P < 0.01) acetic acid molar proportions than STM-S. Rumen fluid from steers supplemented with HTM had a greater (P < 0.03) total VFA than STM-RF at 24 h post incubation. After 12 h post incubation, the molar proportion of propionic acid in HTM-RF was lesser (P = 0.04) than in STM-RF. After simulated abomasal digestion, soluble Mn concentration in HTM-S was greater (P < 0.01) than in STM-S. These data indicate that the source of TM can influence in vitro rumen fermentation characteristics and Mn solubility under simulated abomasal conditions.
Examining the “unearthly archives”: Spiritualism, Psychical Research, and Psychometric Material Culture in the US and Britain
Authors: Hunnicutt Rachel H R
Published: October 2024

This article examines the intersection of material culture and the occult by exploring the practice of psychometry, drawing parallels between this esoteric mode of object interpretation and more conventional approaches. Coined by physician Joseph Rodes Buchanan in the 1840s, psychometry—meaning “soul or mind measurement”—is the ability of “sensitive” individuals, often women, to read an object’s electrical vibration and glean information about its history, as well as that of its owner, living or deceased. Adopted by spiritualists and psychical researchers in the United States and Britain, psychometry mediated between humans and objects, and humans and their own mortality, in the decades spanning the turn of the twentieth century. Drawing on material culture studies, consumer studies, and histories of spiritualism and psychical research, I contextualize and compare firsthand accounts of psychometric readings with more traditional approaches to object-based inquiry to contend that psychometry is a mode of affective design historical practice, a speculative design history that relies on senses other than vision, and knowledge more intuitive than rational.
Machine learning algorithm approach to complete blood count can be used as early predictor of COVID-19 outcome
Authors: Ramalho-Pinto Cecília Horta , Ventura Lucas Haniel Araújo , Camatta Giovanna Caliman , Silveira-Nunes Gabriela , Gomes Matheus Souza , Sato Hugo Itaru , Costa Murilo Soares , Guimarães Henrique Cerqueira , Barbuto Rafael Calvão , Martins-Filho Olindo Assis , Amaral Laurence Rodrigues , Bertarini Pedro Luiz Lima , Teixeira Santuza Maria Ribeiro , Tupinambás Unaí , Teixeira-Carvalho Andrea , Faria Ana Maria Caetano
Published: October 2024

Although the SARS-CoV-2 infection has established risk groups, identifying biomarkers for disease outcomes is still crucial to stratify patient risk and enhance clinical management. Optimal efficacy of COVID-19 antiviral medications relies on early administration within the initial 5 d of symptoms, assisting high-risk patients in avoiding hospitalization and improving survival chances. The complete blood count (CBC) can be an efficient and affordable option to find biomarkers that predict the COVID-19 prognosis due to infection-induced alterations in various blood parameters. This study aimed to associate hematological parameters with different COVID-19 clinical forms and utilizes them as disease outcome predictors. We performed a CBC in blood samples from 297 individuals with COVID-19 from Belo Horizonte, Brazil. Statistical analysis, as well as ROC Curves and machine learning Decision Tree algorithms were used to identify correlations, and their accuracy, between blood parameters and disease severity. In the initial 4 d of infection, traditional hematological COVID-19 alterations, such as lymphopenia, were not yet apparent. However, the monocyte percentage and granulocyte-to-lymphocyte ratio (GLR) proved to be reliable predictors for hospitalization, even in cases where patients exhibited mild symptoms that later progressed to hospitalization. Thus, our findings demonstrate that COVID-19 patients with monocyte percentages lower than 7.7% and a GLR higher than 8.75 are assigned to the hospitalized group with a precision of 86%. This suggests that these variables can serve as important biomarkers in predicting disease outcomes and could be used to differentiate patients at hospital admission for managing therapeutic interventions, including early antiviral administration. Moreover, they are simple parameters that can be useful in minimally equipped health care units.
The lifespan of corpora lutea in nonpregnant females is positively correlated with gestation length
Authors: Lough-Stevens Michael , Ghione Caleb R , Dean Matthew D
Published: October 2024

In mammals, a temporary endocrine gland called the corpus luteum forms on the ovary shortly after ovulation and is required for the initiation and maintenance of early pregnancy. However, the corpus luteum persists even when fertilization or pregnancy does not occur, and species-specific variation in the length of this persistence remains enigmatic. Here we perform a comparative evolutionary study across 72 species and show that corpus luteum lifespan in nonpregnant females is positively correlated with gestation length. We argue that the most likely explanation for this correlation is physiological inertia. The corpus luteum begins secreting progesterone prior to implantation, and when pregnancy does not occur it takes time for females to degrade it and prepare the next reproductive cycle. Our study suggests that this physiological inertia is stronger in species with long gestation times.
Extreme-value modelling of migratory bird arrival dates: Insights from citizen science data
Authors: Koh Jonathan , Opitz Thomas
Published: October 2024

Citizen science mobilises many observers and gathers huge datasets but often without strict sampling protocols, resulting in observation biases due to heterogeneous sampling effort, which can lead to biased predictions. We develop a spatiotemporal Bayesian hierarchical model for bias-corrected estimation of arrival dates of the first migratory bird individuals at their breeding sites. Higher sampling effort could be correlated with earlier observed dates. We implement data fusion of two citizen-science datasets with fundamentally different protocols (BBS, eBird) and obtain posterior distributions of the latent process, which contains four spatial components endowed with Gaussian process priors: species niche; sampling effort; position and scale parameters of annual first arrival date. The data layer consists of four response variables: counts of observed eBird locations (Poisson); presence-absence at observed eBird locations (Binomial); BBS occurrence counts (Poisson); first arrival dates (Generalised Extreme-Value). We devise a Markov Chain Monte Carlo scheme and check by simulation that the latent process components are identifiable. We apply our model to several migratory bird species in the northeastern United States for 2001−2021 and find that the sampling effort significantly modulates the observed first arrival dates. We exploit this relationship to effectively bias-correct predictions of the true first arrivals.
Broncho biliary fistula, a rare complication after hepatectomy: case report of endoscopic and radiological management
Authors: El Ouali Ibtissam I E , El Graini Soumiya S E , El Aoufir Omar O E , Belaabed Soufya S B , Benkabbou Amine A B , Amrani Laila L A , Bakkar Meriem M B , Omor Youssef Y O , Lahnaoui Oumaima O L , Amalik Sanae S A
Published: October 2024

Bronchobiliary fistula (BBF) is one of the most exceptional complications following hepatic surgery. By integrating evidence-based case studies from existing literature, this review offers critical insights into the efficacy of diverse imaging modalities and therapeutic approaches across a broad spectrum of clinical scenarios. Computed tomography, and magnetic resonance cholangiography or even scintigraphy shows an abnormal tractus between biliary ducts and pulmonary bronchi and minimally invasive techniques using endoscopy are considered the techniques of choice. Surgery should only be considered in complicated cases due to significant morbidity and mortality rate. We report the case of a 46-year-old man with metastatic adenocarcinoma of the rectum involving the liver, treated with metastasectomy, which was complicated by a BBF. The patient underwent radiological external drainage followed by endoscopic placement of biliary endoprosthesis with favorable outcome.
Antiglomerular basement membrane disease
Authors: Segelmark Mårten , Hellmark Thomas
Published: October 2024

Antiglomerular basement membrane (anti-GBM) disease, also known as Goodpasture’s disease, is a rare autoimmune kidney and/or lung disease typically caused by autoantibodies directed against the noncollagenous, C-terminal domain of the α3 chain of type IV collagen (α3(IV)NC1). Epidemiology—bimodal age distribution with peaks in the third and sixth/seventh decades; incidence 0.5 to 2/million population/year. Clinical features—typically presents with isolated, rapidly progressive glomerulonephritis but can also present as a renopulmonary syndrome with the combination of glomerulonephritis and lung haemorrhage, or as isolated lung haemorrhage. Pathology—light microscopy typically reveals crescent formation, often in more than 80% of glomeruli, with linear staining of IgG along the GBM. Management—aside from supportive care, this typically consists of (1) stopping the inflammatory process with high doses of corticosteroid, (2) removal of the pathogenic antibodies by plasma exchange, and (3) stopping production of new antibodies with cyclophosphamide. It is controversial whether patients presenting with dialysis dependency and no pulmonary disease benefit from immunosuppression. Imlifidase, a cysteine protease that cleaves the heavy chains of all human IgG subclasses, has shown promise in an open-label phase 2a clinical study. Prognosis—recent series report mortality at 6 to 12 months of 7 to 36%, with patients’ survival mainly dependent on age and renal function at diagnosis. The most important factor in renal prognosis is the glomerular filtration rate at diagnosis, which is strongly correlated to the proportion of crescents seen in the renal biopsy. Very few patients with dialysis dependency at diagnosis regain enough function to become dialysis independent (0–20% most series). Patients do not need long-term immunosuppression, and the disease rarely recurs. Renal transplantation is safe if performed after autoantibodies have been suppressed or naturally disappeared.
Functional Optimization in Distinct Tissues and Conditions Constrains the Rate of Protein Evolution
Authors: Usmanova Dinara R , Plata Germán , Vitkup Dennis
Published: October 2024

Understanding the main determinants of protein evolution is a fundamental challenge in biology. Despite many decades of active research, the molecular and cellular mechanisms underlying the substantial variability of evolutionary rates across cellular proteins are not currently well understood. It also remains unclear how protein molecular function is optimized in the context of multicellular species and why many proteins, such as enzymes, are only moderately efficient on average. Our analysis of genomics and functional datasets reveals in multiple organisms a strong inverse relationship between the optimality of protein molecular function and the rate of protein evolution. Furthermore, we find that highly expressed proteins tend to be substantially more functionally optimized. These results suggest that cellular expression costs lead to more pronounced functional optimization of abundant proteins and that the purifying selection to maintain high levels of functional optimality significantly slows protein evolution. We observe that in multicellular species both the rate of protein evolution and the degree of protein functional efficiency are primarily affected by expression in several distinct cell types and tissues, specifically, in developed neurons with upregulated synaptic processes in animals and in young and fast-growing tissues in plants. Overall, our analysis reveals how various constraints from the molecular, cellular, and species’ levels of biological organization jointly affect the rate of protein evolution and the level of protein functional adaptation.
Gentrius: Generating Trees Compatible With a Set of Unrooted Subtrees and its Application to Phylogenetic Terraces
Authors: Chernomor Olga , Elgert Christiane , von Haeseler Arndt
Published: October 2024

For a set of binary unrooted subtrees generating all binary unrooted trees compatible with them, i.e. generating their stand, is one of the classical problems in phylogenetics. Here, we introduce Gentrius—an efficient algorithm to tackle this task. The algorithm has a direct application in practice. Namely, Gentrius generates phylogenetic terraces—topologically distinct, equally scoring trees due to missing data. Despite stand generation being computationally intractable, we showed on simulated and biological datasets that Gentrius generates stands with millions of trees in feasible time. We exemplify that depending on the distribution of missing data across species and loci and the inferred phylogeny, the number of equally optimal terrace trees varies tremendously. The strict consensus tree computed from them displays all the branches unaffected by the pattern of missing data. Thus, by solving the problem of stand generation, in practice Gentrius provides an important systematic assessment of phylogenetic trees inferred from incomplete data. Furthermore, Gentrius can aid theoretical research by fostering understanding of tree space structure imposed by missing data.
Evolutionary Dynamics of Proinflammatory Caspases in Primates and Rodents
Authors: Holland Mische , Rutkowski Rachel , C. Levin Tera
Published: October 2024

Caspase-1 and related proteases are key players in inflammation and innate immunity. Here, we characterize the evolutionary history of caspase-1 and its close relatives across 19 primates and 21 rodents, focusing on differences that may cause discrepancies between humans and animal studies. While caspase-1 has been retained in all these taxa, other members of the caspase-1 subfamily (caspase-4, caspase-5, caspase-11, and caspase-12 and CARD16, 17, and 18) each have unique evolutionary trajectories. Caspase-4 is found across simian primates, whereas we identified multiple pseudogenization and gene loss events in caspase-5, caspase-11, and the CARDs. Because caspase-4 and caspase-11 are both key players in the noncanonical inflammasome pathway, we expected that these proteins would be likely to evolve rapidly. Instead, we found that these two proteins are largely conserved, whereas caspase-4's close paralog, caspase-5, showed significant indications of positive selection, as did primate caspase-1. Caspase-12 is a nonfunctional pseudogene in humans. We find this extends across most primates, although many rodents and some primates retain an intact, and likely functional, caspase-12. In mouse laboratory lines, we found that 50% of common strains carry nonsynonymous variants that may impact the functions of caspase-11 and caspase-12 and therefore recommend specific strains to be used (and avoided). Finally, unlike rodents, primate caspases have undergone repeated rounds of gene conversion, duplication, and loss leading to a highly dynamic proinflammatory caspase repertoire. Thus, we uncovered many differences in the evolution of primate and rodent proinflammatory caspases and discuss the potential implications of this history for caspase gene functions.
Reappraisal of prognostic factors in CNS WHO grade 3 oligodendrogliomas IDH-mutant and 1p/19q co-deleted: Lessons from the French POLA cohort
Authors: Figarella-Branger Domique , Colin Carole , Mokhtari Karima , Uro-Coste Emmanuelle , Idbaih Ahmed , Appay Romain , Tabouret Emeline , Touat Mehdi , Seyve Antoine , Carpentier Catherine , Dehais Caroline , Ducray François ,   the POLA network, Desenclos C , Guillain N , Menei P , Rousseau A , Cruel T , Lopez S , Abad M , Hamdan N , Adam C , Parker F , Seizeur R , Quintin-Roué I , Chotard G , Bronnimann C , Ricard D , Godfraind C , Khallil T , Cazals-Hatem D , Faillot T , Gaultier C , Tortel MC , Carpiuc I , Richard P , Aubriot-Lorton H , Ghiringhelli F , Djelad A , Maurage CA , Gueye EM , Labrousse F , Ducray F , Meyronet D , Figarella-Branger D , Chinot O , Bauchet L , Rigau V , Gauchotte G , Taillandier L , Campone M , Loussouarn D , Bourg V , Vandenbos-Burel F , Guillamo J-S , Roger P , Blechet C , Adle-Biassette H , Bielle F , Carpentier A , Dehais C , Milin S , Wager M , Colin P , Diebold MD , Chiforeanu D , Vauleon E , Marguet F , Langlois O , Forest F , Motso-Fotso MJ , Andraud M , Khettab M , Lhermitte B , Noel G , Bernier M , Younan N , Rousselot-Denis C , Zemmoura I , Joubert C , Cohen-Moyal E , Uro-Coste E , Dhermain F
Published: October 2024

Background

In the POLA cohort, 3 pathological groups of CNS WHO grade 3 oligodendroglioma IDH-mutant and 1p/19q co-deleted have been described: group 1 (high mitotic count only), group 2 (microvascular proliferation MVP and no necrosis), and group 3 (MVP and necrosis).

Methods

494 patients from the POLA cohort, with a median follow-up of 96 months were included. To identify the impact of the pathological groups and contrast enhancement (CE) in group 1 on overall survival (OS) or progression-free survival (PFS), survival curves were obtained (Kaplan–Meier method) and compared (log-rank test). The prognostic value of clinical factors and CDKN2A homozygous deletion HD were also tested. Multivariate analysis was performed.

Results

Survival analysis demonstrated that the pathological groups were associated with both progression-free survival (PFS P = .01) and overall survival (OS P = .001). In group 1, patients with CE (1CE+) had a poorer prognosis compared to those without (OS P = .028, PFS P = .006). Further stratification into group 1CE−, group 1CE+, group 2, and group 3 provided clearer prognostic distinctions (OS P = .002, PFS P < .0001). Other prognostic factors included age (OS P < .0001, PFS P = .002), extent of surgical resection (OS P = .001, PFS P = .003), KPS (OS P < .0001, PFS P = 0.002), postoperative treatment (OS P = .007, PFS P < .0001), and CDKN2A HD (OS and PFS P < .0001). The pathological groups remained of prognostic significance for PFS in multivariate analysis.

Conclusions

Necrosis and CDKN2A HD are adverse prognostic factors of WHO grade 3 oligodendrogliomas, IDH-mutant, and 1p/19q co-deleted. Besides, in group 1 patients, lack of CE is a factor of better prognosis.
The leucine-rich repeat receptor kinase QSK1 regulates PRR-RBOHD complexes targeted by the bacterial effector HopF2Pto
Authors: Goto Yukihisa , Kadota Yasuhiro , Mbengue Malick , Lewis Jennifer D , Matsui Hidenori , Maki Noriko , Ngou Bruno Pok Man , Sklenar Jan , Derbyshire Paul , Shibata Arisa , Ichihashi Yasunori , Guttman David S , Nakagami Hirofumi , Suzuki Takamasa , Menke Frank L H , Robatzek Silke , Desveaux Darrell , Zipfel Cyril , Shirasu Ken
Published: October 2024

Plants detect pathogens using cell-surface pattern recognition receptors (PRRs) such as ELONGATION Factor-TU (EF-TU) RECEPTOR (EFR) and FLAGELLIN SENSING 2 (FLS2), which recognize bacterial EF-Tu and flagellin, respectively. These PRRs belong to the leucine-rich repeat receptor kinase (LRR-RK) family and activate the production of reactive oxygen species via the NADPH oxidase RESPIRATORY BURST OXIDASE HOMOLOG D (RBOHD). The PRR-RBOHD complex is tightly regulated to prevent unwarranted or exaggerated immune responses. However, certain pathogen effectors can subvert these regulatory mechanisms, thereby suppressing plant immunity. To elucidate the intricate dynamics of the PRR-RBOHD complex, we conducted a comparative coimmunoprecipitation analysis using EFR, FLS2, and RBOHD in Arabidopsis thaliana. We identified QIAN SHOU KINASE 1 (QSK1), an LRR-RK, as a PRR-RBOHD complex-associated protein. QSK1 downregulated FLS2 and EFR abundance, functioning as a negative regulator of PRR-triggered immunity (PTI). QSK1 was targeted by the bacterial effector HopF2Pto, a mono-ADP ribosyltransferase, reducing FLS2 and EFR levels through both transcriptional and transcription-independent pathways, thereby inhibiting PTI. Furthermore, HopF2Pto transcriptionally downregulated PROSCOOP genes encoding important stress-regulated phytocytokines and their receptor MALE DISCOVERER 1-INTERACTING RECEPTOR-LIKE KINASE 2. Importantly, HopF2Pto requires QSK1 for its accumulation and virulence functions within plants. In summary, our results provide insights into the mechanism by which HopF2Pto employs QSK1 to desensitize plants to pathogen attack.
Mechanistic effects of lipid binding pockets within soluble signaling proteins: lessons from acyl-CoA-binding and START-domain-containing proteins
Authors: Lung Shiu-Cheung , Chye Mee-Len
Published: October 2024

While lipids serve as important energy reserves, metabolites, and cellular constituents in all forms of life, these macromolecules also function as unique carriers of information in plant communication given their diverse chemical structures. The signal transduction process involves a sophisticated interplay between messengers, receptors, signal transducers, and downstream effectors. Over the years, an array of plant signaling proteins have been identified for their crucial roles in perceiving lipid signals. However, the mechanistic effects of lipid binding on protein functions remain largely elusive. Recent literature has presented numerous fascinating models that illustrate the significance of protein–lipid interactions in mediating signaling responses. This review focuses on the category of lipophilic signaling proteins that encompass a hydrophobic binding pocket located outside of cellular membranes and provides an update on the lessons learned from two of these structures, namely the acyl-CoA–binding and steroidogenic acute regulatory protein-related lipid transfer domains. It begins with a brief overview of the latest advances in understanding the functions of the two protein families in plant communication. The second part highlights five functional mechanisms of lipid ligands in concert with their target signaling proteins.
Competition and Certification: Theory and Evidence from the Audit Market
Authors: Geng Heng (Griffin) , Zhang Cheng , Zhou Frank S
Published: October 2024

We study how financial certifier competition influences loan contracting in the context of financial auditing. Exploiting the unexpected demise of Arthur Andersen that exogenously decreased auditor competition, we find a greater decrease in loan spread for borrowers in markets in which certifier competition declined more. Additional analyses suggest the result stems from enhanced audit quality and reduced credit risk. The effect of certifier competition is stronger for borrowers with weaker external monitoring and those generating significant revenue for their auditors. Our evidence highlights negative consequences of financial certifier competition. (JEL D43, G21, M42, M49)
RSPO/LGR signaling regulates proliferation of adult hippocampal neural stem cells
Authors: Valenzuela-Bezanilla Daniela , Mardones Muriel D , Galassi Maximiliano , Arredondo Sebastian B , Santibanez Sebastian H , Gutierrez-Jimenez Stephanie , Merino-Véliz Nicolás , Bustos Fernando J , Varela-Nallar Lorena
Published: October 2024

In the dentate gyrus of the adult hippocampus, neurogenesis from neural stem cells (NSCs) is regulated by Wnt signals from the local microenvironment. The Wnt/β-catenin pathway is active in NSCs, where it regulates proliferation and fate commitment, and subsequently its activity is strongly attenuated. The mechanisms controlling Wnt activity are poorly understood. In stem cells from adult peripheral tissues, secreted R-spondin proteins (RSPO1-4) interact with LGR4-6 receptors and control Wnt signaling strength. Here, we found that RSPO1-3 and LGR4-6 are expressed in the adult dentate gyrus and in cultured NSCs isolated from the adult mouse hippocampus. LGR4-5 expression decreased in cultured NSCs upon differentiation, concomitantly with the reported decrease in Wnt activity. Treatment with RSPO1-3 increased NSC proliferation and the expression of Cyclin D1 but did not induce the expression of Axin2 or RNF43, 2 well-described Wnt target genes. However, RSPOs enhanced the effect of Wnt3a on Axin2 and RNF43 expression as well as on Wnt/β-catenin reporter activity, indicating that they can potentiate Wnt activity in NSCs. Moreover, RSPO1-3 was found to be expressed by cultured dentate gyrus astrocytes, a crucial component of the neurogenic niche. In co-culture experiments, the astrocyte-induced proliferation of NSCs was prevented by RSPO2 knockdown in astrocytes and LGR5 knockdown in hippocampal NSCs. Additionally, RSPO2 knockdown in the adult mouse dentate gyrus reduced proliferation of neural stem and progenitor cells in vivo. Altogether, our results indicate that RSPO/LGR signaling is present in the dentate gyrus and plays a crucial role in regulating neural precursor cell proliferation.